Ionizing Radiation Ebooks Catalog

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Treatment Implications Ionizing Radiation

Exposure to ionizing radiation (IR) results in DNA damage, most significantly DSBs. In normal cells, DNA damage induces cell cycle arrest to prevent the spread of deleterious cells and activates repair pathways to correct genomic defects. IR as the basis of radiotherapy is a standard treatment used against cancer and is indicated for approximately 60 of cancer patients (41). Yet, even though it is an important cancer therapy, improving outcomes after radiation therapy remains an important clinical goal. To date, certain biologically targeted therapies have been shown to enhance radiation response. However, currently available agents are targeted to specific gene mutations and benefit only a small subset of patients with solid tumors (41). The ideal radiosensitizer then should be relatively nontoxic and enhance the clinical effectiveness of IR in a broad range of tumors. Are there aspects of BRCA1 and BRCA2 function that might impact radiation treatment

Ionizing Radiation

Acute high dose radiation (> 250 rads). An acute overdose of ionizing radiation during pregnancy can cause fetal microcephaly, mental retardation, growth retardation, and leukemia. After exposure to more than 25 rads, classic fetal defects will be observed termination of pregnancy should be offered as an option. Much information concerning acute high-dose radiation has come from studies of the atomic explosions over Hiroshima and Nagasaki.

Radiation Exposure in Humans

After the war, a joint Japanese-U.S. effort was made to study the biological effects of radiation exposure on the survivors of the atomic blasts and their children. Somatic mutations were examined by studying radiation sickness and cancer among the survivors germ-line mutations were assessed by looking at birth defects, chromosome abnormalities, and gene mutations in children born to people that had been exposed to radiation. Geneticist James Neel and his colleagues examined almost 19,000 children of parents who were within 2000 meters of the center of the atomic blast at Hiroshima or Nagasaki, along with a similar number of children whose parents did not receive radiation exposure. Radiation doses were estimated for the child's parents on the basis of careful assessment of the parents' location, posture, and position at the time of the blast. A blood sample was collected from each child, and gel electrophoresis was used to investigate amino acid substitutions in 28 proteins. When...

Diagnosis of deepvein thrombosis Introduction

The diagnosis of venous thrombosis in pregnancy can be challenging because (1) unilateral left leg swelling can be caused by compression of the left iliac vein by the gravid uterus (2) leg swelling can be caused by isolated common iliac vein thrombosis that may not be detectable by CUS, and (3) venographic examination of pelvic veins is problematic because ofirradiation risk to the foetus. CUS is the initial test of choice in all patients, and the use of venography is limited to patients with suspected isolated iliac vein thrombosis, when the vein cannot be identified by CUS. Although venography exposes the foetus to irradiation, the risk of a fatal pulmonary embolism from a missed iliac thrombus probably outweighs the risk of radiation exposure to the foetus. Examination of the external and common iliac veins is technically feasible in the first two trimesters and can sometimes be done even in the third trimester with appropriate positioning. As in non-pregnant women, patients who...

Risks of Radiological Procedures

The terrifying experiences of the early x-ray pioneers, some of their patients, and the victims of Hiroshima, Nagasaki, and Chernobyl demonstrate the risks of exposure to large doses of ionizing radiation with dire clarity. However, the number of human beings who have been helped by the use of radiation in diagnosis and therapy exceeds that of the victims by several orders of magnitude. The injuries that can be induced by the normal procedures in diagnostic radiology are less frequent and less severe than those that occur in the course of other routine medical therapies (for example, drug intoxications) or other diagnostic procedures (for example, pancreatitis after ERCP). All the same, many patients continue to feel uneasy about x rays. They need to be comforted with truthful information, and we need to strive to limit the use of diagnostic ionizing radiation to proper indications.

Effect Does Not Equal Effect

Stochastic effect Even minimal radiation doses have an effect. They increase the likelihood of developing malignant tumors (somatic effect) and sustaining genetic damage (genetic effect) that might otherwise also occur without interference by man-made technology though less frequently. There are therefore no real threshold values below which the administration of x-rays is totally safe. This effect is also called the stochastic effect. It is a fundamental effect associated with the use of all ionizing radiation in diagnostic radiology and the major reason for the general radiation protection efforts today. a pioneer of intrathoracic surgery, tried to save him with a last-minute operation but was unsuccessful. A large-bowel carcinoma as one likely cause of the ileus could only be attributed to the stochastic effect. X-ray tubes were prohibitively expensive even in those early days and they survived but a few exposures. For that reason R ntgen's total radiation exposure was probably...

Nuclear Magnetic Resonance Spectroscopy

Sures the absorbance of radio frequency electromagnetic energy by certain atomic nuclei. NMR-active isotopes of biologically relevant atoms include H, 13C, 15N, and 31P. The frequency, or chemical shift, at which a particular nucleus absorbs energy is a function of both the functional group within which it resides and the proximity of other NMR-active nuclei. Two-dimensional NMR spectroscopy permits a three-dimensional representation of a protein to be constructed by determining the proximity of these nuclei to one another. NMR spectroscopy analyzes proteins in aqueous solution, obviating the need to form crystals. It thus is possible to observe changes in conformation that accompany lig-and binding or catalysis using NMR spectroscopy. However, only the spectra of relatively small proteins, < 20 kDa in size, can be analyzed with current technology.

Working With What You Have Tactics To Augment The Oncolytic Ability Of y1345 Mutant Derivatives

Although y134.5 mutant derivatives appeared safe in preclinical animal studies, their restricted replication resulting from their inability to counter components of the innate host response needed to be addressed if they were to emerge as efficacious oncolytic agents. One approach to deal with this concern combines conventional chemotherapy and radiotherapy with oncolytic virus treatment of mice with human tumor implants, taking advantage of specific properties associated with each treatment modality (46-50). On the one hand, traditional systemic treatments, although highly toxic, are able to effectively debulk a tumor. Oncolytic y 4.5 mutant derivatives, on the other hand, appear safe but have limited replicative ability in many human tumor cells. The question at hand then, was if the two therapeutic components together were more effective than each individual component. In support of this idea, head and neck derived squamous cell carcinomas implanted into mice subcutaneously and...

Pathophysiology Of Cold Injuries

Heat is lost through the following four mechanisms radiation, convection, conduction, and evaporation. Radiation, in which heat is transferred by electromagnetic waves, accounts for almost two-thirds of heat loss in a cold environment. Radiant heat loss can be minimized by wearing appropriate warm clothing and minimizing the body surface area exposed to the cold environment. Conduction refers to the transfer of heat from warmer to cooler objects by direct contact. Heat loss through this mechanism is usually minimal, but it becomes a major source of heat loss in wet clothes or with cold-water immersion. Convection is the loss of heat to surrounding air and water vapor. Heat loss by convection is dependent on a combination of environmental factors, including wind velocity and temperature. The wind chill index, which estimates the equivalent temperature effect on exposed skin, is a combination of the ambient temperature and the wind velocity. It is a more important consideration than the...

Magnetic Resonance Imaging

The advantages of MRI include the lack of ionizing radiation and the ability to scan without an iodinated contrast agent. Inherent tissue contrast on T1- and T2-weighted images and the use of proper imaging pulse sequences often allow lesion detection and characterization without the use of contrast agent. However, gadolinium chelates and new tissue-specific contrast agents further improve lesion detection and characterization (Semelka and Helmberger, 2001). The major limitations of abdominal

The Genotoxic Mechanism

Growth Factor-Induced Cell Proliferation. Hormones. Rodent thyroid follicular cell tumor in contrast to human thyroid tumors that are mostly induced by ionizing radiation, thyroid follicular cell tumors in rodents are induced by genotoxic or nongenotoxic carcinogens. Several nongenotoxic chemicals (such as perchlorate, thiorueas, lithium, lupiditine) are known to perturb the balance of the thyroid stimulating hormone (TSH) in rodents. These chemicals are referred to as goitrogens and their modes of action are different. They may deplete iodine accumulation by inhibiting iodine trapping in the thyroid or by blocking binding of iodine and coupling of iodothyronine to form thyroxine and triiodothyronine. Alternately, they may inhibit thyroid hormone secretion by pro-teolysis or enhance metabolism of thyroxine by inducing liver metabolic enzymes (78). Disruption of thyroxine function activates the pituitary-thyroid feedback mechanism, which increases the production of TSH. An increase...

Component Reference Methods

Total body potassium can also be measured using dilution of the radioactive isotope 42K (7). This method is useful in specialized whole-body counter calibration studies, but has no practical application in the study of human obesity. The 12.4-hr half-life of 42K and the radiation exposure involved preclude the routine use of

Environment as determinant of i genotype and ii disease

Second, the environment presents many exposures that directly alter the probability of occurrence of various diseases. Ionizing radiation contributes to the risks of breast cancer and leukemia. Asbestos causes asbestosis and mesothelioma. Environmental tobacco smoke increases the risks of lung cancer and coronary heart disease. Heavy metals induce various forms of organ dysfunction, for example, environmental lead exposure in early childhood impairs neurocogni-tive development. Patterns of exposure to various antigens in early childhood influence the maturation path of the young immune system, and also

Other Imaging Modalities

There are applications when it is not practical to use the mammogram for assessment of breast density and instead, it is preferable to use another imaging method for this purpose. One example is in young women (under age 40) who do not normally receive routine mammograms. Another may be in high-risk women where it maybe advisable to monitor changes in the breast more frequently than is considered appropriate with mammography. In both cases, an imaging method that does not employ ionizing radiation would be desirable. Two modalities can be immediately considered ultrasound and magnetic resonance imaging. Not only do these avoid radiation concerns, but they also produce three-dimensional image data, thereby facilitating volumetric analysis.

Pet Experimental Design And Data Analysis

The range of experimental design strategies for PET is limited by the physical constraints associated with delivering and measuring radioisotopes. At a minimum, 150 studies involve an aggregation of activity occurring over 30 seconds or more, and for metabolism and neurotransmitter studies the aggregation covers 20 to 60 minutes. This temporal resolution precludes event-related types of designs and makes it difficult to dissociate the different processes involved in a task. The total number of radiotracer injections (and hence scans) is limited by radiation exposure and the need to allow previously administered radiotracers to decay substantially before starting the next scan (this takes hours for nC and 18F and about 8 to 10 minutes for 150). With 150, one is typically limited to about 12 scans in a 2-hour scanning session, and with 18F and nC, one is typically limited to 2 to 4 scans (usually scheduled on different days because the subjects would need to spend hours waiting for the...

Multiple Myeloma 21 Epidemiology

Hematologic malignancies.6 A declining immune system and increased accumulation of certain chemicals and toxins, such as herbicides, insecticides, asbestosis, and rubber, plastic, wood, or petroleum products, may increase susceptibility among older individuals or people with increased occupational exposure.11,12 Radiation exposure from the atomic bomb in Hiroshima and Nagasaki, or occupation related in nuclear plant workers or radiologists also increases the risk.13

Tandem Mass Spectrometry

Fig. 6.3 Tandem in time MS systems implemented as (a) 3D ion trap or (b) 2D (linear) ion trap. In the central part of these analyzers, the ions are trapped, selectively fragmented, and mass-analyzed by dynamic electromagnetic fields in the presence of a mediator collision gas (mostly He). Fig. 6.3 Tandem in time MS systems implemented as (a) 3D ion trap or (b) 2D (linear) ion trap. In the central part of these analyzers, the ions are trapped, selectively fragmented, and mass-analyzed by dynamic electromagnetic fields in the presence of a mediator collision gas (mostly He).

Biology of DNA Repair in Tumor Cells and Normal Cells

One of the main advantages of brachytherapy is related to the radiation biology of continuous low-dose irradiation, which tends to substantially damage proliferating tumor cells while allowing normal tissue a chance for repair of sublethal damage (19,21,22,24,30). Normal tissue is more efficient at repairing the sublethal damage, but as the dose rate increases there is less separation of this effect the higher the dose rate, the lower is the total dose at which damage to normal tissue is observed. Cells commonly respond to DNA damage from ionizing radiation by activating cell-cycle checkpoints. These checkpoints permit cells to correct possible DNA damage before proceeding through the cell cycle. Ionizing radiation induces arrest in the Gj, S, and G2 phases of the cell cycle (31). In addition, cell survival data have shown that cells are most sensitive to radiation during mitosis and G2, are less sensitive in G1, and are least sensitive during the latter part of S phase (32,33)....

Microwave Coagulation Therapy

Microwave coagulation therapy (MCT) uses dithermic heat energy to cause thermal coagula-tive necrosis. MCT utilizes a much higher frequency electromagnetic field. Polarization of water molecules in the alternating electromagnetic field leads to heating of intracellular water. The higher frequency energy allows for more localized energy but, as is the problem with other thermal techniques, causes reduction in tissue penetration. The therapy can be delivered during laparotomy, laparoscopy, or by a percutaneous approach.

Body Fat Distribution

However, there is not yet sufficient evidence on the relationship between these indices and visceral fat to justify ethnic specific cutoff points for body fat distribution (58-61), and there is not yet enough information about the relation with these indices with morbidity. Generally African-Americans (children as well as adults) have less visceral adipose tissue as found by CT or MRI than their white counterparts (59,60,62,63). On the other hand, a comparative study among Pima Indians showed that there were no differences in visceral and subcutaneous abdominal fat areas (MRI) with age-, sex-, and BMI-matched Caucasians (64). The main limitation of most studies is the relatively small number of subjects, due to the nature (cost and radiation exposure) of the measurements. Data from NHANES III (65) show that for the same level of apparent body fatness (BMI) the corresponding WC values are higher in Caucasians than in Hispanics and African-Americans. This seems contradictive to the fact...

Telomeric Rearrangements

Chromosomal anomalies may be numerical or structural. Structural changes result from the breakage and rearrangement of chromosome parts, and animal experiments have shown that they can be induced by a variety of exposures, including ionizing radiation and certain viral infections and toxic substances. They occur as duplications, deletions, translocations, insertions, or inversions of chromosome parts or as rings on selected chromosomes. Numerical anomalies arise through nondisjunction during meiosis or mitosis, through lagging of chromosomes at anaphase of cell division, or through fertilization by two sperm (i.e., triploidy). Chromosomal anomalies as a whole contribute more to fetal loss than to live births and MR. Kline, Stein, and Susser (1989) estimated that from 8 weeks after the last menstrual period, the proportion of chromosomal aberrations lost by miscarriage exceeds 90 for all but trisomy 21 (DS), XXX, XXY (Klinefelter syndrome), and XYY. In survivors after birth in...

Gene Replacement Therapy

Roth et al. (33) were the first group to demonstrate the safety and feasibility of using a retroviral wt-p53 construct in patients with advanced NSCLC. Currently there are several ongoing trials using adenoviral-mediated p53-based gene therapy for human cancers of the lung, brain, ovary, head and neck, and bladder (34-38). Similar trials have previously shown that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumor regression in patients with advanced NSCLC and recurrent head and neck cancer (36). Based on these reports, Swisher et al. (39) extended their previous studies of Ad-p53 as a single agent in NSCLC and initiated a clinical trial of Ad-p53 combined with external beam ionizing radiation. These investigators reported that intratumoral injection of Ad-p53 followed by radiation therapy was well tolerated, led to successful p53 gene transfer, had low toxicity, and produced tumor regression. A high metastatic...

Posttranslational regulation signaling of DNA damage

The main regulator of p53 protein activity is Mdm-2, a protein that binds p53 in the N-terminus (residues 17-29), conceals its transcription activation domain, redirects p53 from nucleus to cytoplasm and acts as an ubiquitin ligase to target p53 for degradation by the proteasome. The MDM2 gene is a transcriptional target of p53, thus defining a feedback loop in which p53 controls its own stability (Moll and Petrenko, 2003). The p53 Mdm-2 complex is regulated by p14Arf (Alternative Reading Frame), a 14 kD protein encoded by an alternative reading frame of CDKN2A, the gene that encodes the tumor suppressor p16 (Moore et al., 2003). The kinetics, extent and consequences of p53 activation vary according to the nature and intensity of the inducing signals. In response to ionizing radiation, activation of p53 proceeds through phosphorylation of p53 in the N-terminus by kinases involved in DNA-damage sensing, such as Atm (the product of the Ataxia Telangiectasia mutated gene) and Chk2 (a...

Antisense Oligonucleotides

A more recent study examined the feasibility of using adenovirus-mediated, heat-activated expression of antisense Ku70 RNA as a gene therapy approach to sensitize cells and tumors to ionizing radiation. The adenovirus vector contained antisense Ku70 under the control of hsp70 promoter. Their data showed that heat shock induces antisense Ku70 mRNA expression, reduces the endogenous Ku70 expression level, and significantly increases the radiosensitivity of cells. This approach was then extended to in vivo models where heat-shock-induced expression of antisense Ku70 mRNA using this same vector attenuated Ku70 protein expression in murine FSa-II tumors, and radiosensitized the FSa-II tumors (113). Based on these results it appears that adeno-virus-mediated, heat-activated antisense Ku70 expression is a novel approach to radiosensitize human tumors.

Angiogenesis Inhibitors

Over the last years, tumor-specific vasculature formation (angiogenesis) has emerged as a promising new target for inhibiting the growth of tumors (114-118), using antiangio-genic agents either alone, or in combination with conventional therapies (114,115, 117-119). The key advantages of this approach are that because it targets normal endothelial cells rather than tumor cells, the development of drug resistance is less likely (114), and that antiangiogenic therapy can exert a powerful antitumor effect with little or no systemic toxicity to the host (114,115,117,118). The combination of antiangiogenic agents with ionizing radiation has demonstrated a local synergistic antitumor interaction between the two modalities (120-123) for angiostatin (120), antivascular endothelial growth factor antibody (121), and endostatin (122). Several investigators have produced adenoviral based vectors for delivering the genes that encode these or similar proteins thereby enabling future tests of...

Loss of Chromosome 5 or del5q

In primary MDS, abnormalities of chromosome 5 are observed in the 5q- syndrome (described below) or, more commonly, in RAEB 1, 2 of the WHO classification in association with a complex karyotype. Clinically, the patients with del(5q) coupled with other cyto-genetic abnormalities have a poor prognosis with early progression to leukemia, resistance to treatment, and short survival. Abnormalities of 5q are associated with previous exposure to standard and high dose alkylating agent therapy, including use in immunosuppressive regimens (Aul et al. 1998 Larson et al. 1996 McCarthy et al. 1998 Pedersen-Bjergaard et al. 2000). A role for exposure to benzene (Hayes et al. 1997) as well as therapeutic ionizing radiation (Fenaux et al. 1989 Rowley and Olney 2002) as risks for MDS is emerging.

Specific Occupations And Parkinsonism

Occupational exposure to magnetic fields may be a risk factor for PD (70). A death certificate (population-based) case-control study in Colorado, U.S.A. utilizing a tiered exposure matrix found an adjusted odds ratio of 1.76 for PD subjects exposed to magnetic fields. Occupations included in this study were electronic technicians and engineers, repairers of electronic equipment, telephone and telephone line installers and repairers, electric power installers and repairers, supervisors of electricians and power transmission installers, power plant operators, motion picture projectionists, broadcast equipment operators, and electricians (70). Another study of electrical workers in a similar group of occupations found a nonsignificant, elevated odds ratio of 1.1 for PD compared to controls, but the study lacked power (71).

Conventional NMR Spectroscopy

Solution state NMR spectroscopy is the study of molecules by recording the interaction of radiofrequency electromagnetic radiation with the nuclei of molecules in solution when placed in a strong magnetic field. The circulation of electrons around nuclei in different electronic environments creates local magnetic environments. These local magnetic fields give rise to characteristic chemical shifts suitable for functional group identification. Moreover, the presence of coupling between pairs of nuclei extending over 1-3 bonds establishes the connectivity between atoms and provides a powerful tool for structural elucidation including stereochemical information. However, the quantum basis of NMR, first described in 1946 by Bloch and Pur-cell (awarded a Nobel prize in 1952), is beyond the scope of this review. The interested reader is referred to several excellent textbooks on the principles of NMR 20, 21 . Here, the pivotal features that pertain to toxicology are presented in Table 8.1....

Cancer Surveillance And Prevention

Recently the American Cancer Society issued new guidelines for breast screening based on level of risk (89). These recommendations include annual screening with MRI as an adjunct to mammography for women with a 20 to 25 lifetime breast cancer risk, based on evidence accumulated from prospective trials of BRCA mutation carriers, and Expert Consensus Opinion for LFS. The BRCA studies indicated an increased sensitivity, but reduced specificity, for MRI as compared with mammography. Importantly, fewer interval cancers occurred in the annual MRI screening groups. The recommended age to begin MRI and mammography screening was 30 years, although it was noted that consideration should be given to individual factors such as age of breast cancer diagnosis in the family. The use of MRI is particularly appealing for LFS patients, given the previously cited concerns regarding radiation exposure.

Adenosine Deaminase Purine Nucleoside Phosphorylase Deficiency

Unlike the end products of purine catabolism, those of pyrimidine catabolism are highly water-soluble CO2, NH3, P-alanine, and P-aminoisobutyrate (Figure 34-9). Excretion of P-aminoisobutyrate increases in leukemia and severe x-ray radiation exposure due to increased destruction of DNA. However, many persons of Chinese or Japanese ancestry routinely excrete P-aminoisobutyrate. Humans probably transaminate P-aminoisobutyrate to methylmalonate semialdehyde, which then forms succinyl-CoA (Figure 19-2).

Acute Lymphoblastic Leukemia

The etiology of ALL is unknown in the vast majority of cases. Environmental agents, such as ionizing radiation and chemical mutagens, have been implicated, and there is evidence to suggest a genetic factor in some patients. Children with Down syndrome have an increased risk of leukemia, particularly precursor B lymphoblastic leukemia. There is a higher frequency of childhood ALL in industrialized countries compared with in developing countries. It has also been postulated that some cases of childhood leukemia stem from an adverse cellular response to common infections that occur at a later time than was typically experienced in past centuries.45,46 These delayed exposures are believed to increase the risk of genetic mutations in the lymphoid precursors, leading to the development of leukemia.

Management of extremity injury

X-ray facilities are generally designated essential for the diagnosis, treatment and successful outcome of skeletal injuries. It is essential that such facilities be available at appropriate levels in the system, particularly where orthopaedic surgical expertise is available. It is desirable to have X-ray facilities at a lower level (e.g. GP-level hospital or even basic facilities) to facilitate primary diagnosis and decisions regarding transfer of the patient. Portable X-rays assist in the management of patients in traction and during operative procedures. Capabilities for portable X-rays should be essential at the tertiary care level and are desirable at lower-level hospitals. C-arm image intensifier (fluoroscopy) is considered an integral part of the orthopaedic armamentarium in many settings these days as it offers accuracy, reduces operative time, decreases radiation exposure, allows closed procedures and hence saves blood loss and reduces infection rate (37, 38). It is...

Ataxia Telangiectasia Mutated

Individuals homozygous for germline mutations in ataxia telangiectasia mutated (ATM) have ataxia telangiectasia (AT), an autosomal recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasias, radiation hypersensitivity, and an increased incidence of malignancy (29). AT homozygotes have cancer risks 60 to 180 times greater than the general population including non-Hodgkins lymphoma (nearly 100 lifetime risk) and breast and ovarian cancer (30). Heterozygosity for germline mutations in ATM was initially hypothesized by Swift et al. to confer an increased breast cancer risk and that screening mammography, a source of ionizing radiation, could theoretically increase the penetrance of such mutations (31). An initial study supporting the hypothesis was criticized due to the exceptionally low rate of breast cancer among the controls. In addition, subsequent studies did not consistently support a link between ATM mutation heterozygosity and breast cancer...

Biomedical Importance

The genetic information in the DNA of a chromosome can be transmitted by exact replication or it can be exchanged by a number of processes, including crossing over, recombination, transposition, and conversion. These provide a means of ensuring adaptability and diversity for the organism but, when these processes go awry, can also result in disease. A number of enzyme systems are involved in DNA replication, alteration, and repair. Mutations are due to a change in the base sequence of DNA and may result from the faulty replication, movement, or repair of DNA and occur with a frequency of about one in every 106 cell divisions. Abnormalities in gene products (either in protein function or amount) can be the result of mutations that occur in coding or regulatory-region DNA. A mutation in a germ cell will be transmitted to offspring (so-called vertical transmission of hereditary disease). A number of factors, including viruses, chemicals, ultraviolet light, and ionizing radiation,...

Progress Toward Identifying Common Lowpenetrance Alleles

Perhaps the only confirmed low-penetrance breast cancer susceptibility allele identified to date is the 1100delc variant in CHEK2. CHEK2 encodes a G2 checkpoint kinase that plays a critical role in DNA damage repair. It is the human ortholog of the yeast Cdsl and Rad53 G2 checkpoint kinases (19). Activation of these proteins in response to DNA damage prevents cellular entry into mitosis. In mammalian cells, activation of CHEK2 in response to ionizing radiation is regulated through phosphorylation by ATM (20). Activated CHEK2 phosphorylates critical cell-cycle proteins, including p53, Cdc25C, Cdc25A, and BRCA1, promoting cell-cycle arrest and activation of DNA repair (21-24).

Frameworks For Exposure Assessment 21 Concepts and Models of Human Exposure

A 1991 report of the National Research Council offers a useful framework for considering the linkages from pollution sources to exposures to doses and subsequent human health effects (NRC, 1991). In general, pollutant sources are linked to human exposure through the three principal environmental media air, water, and food. Pollutants may contaminate food directly or through transport of the toxic agent by an environmental medium. Food sources often concentrate toxic environmental agents across the food chain, as with the example of methylmercury in fish. In addition to these three media, some agents reach people through direct physical contact, which is how ionizing and non-ionizing radiation, for example, exert their effects. In urban environments, water may be contaminated centrally at treatment facilities or at buildings through aged or contaminated pipes, which may contain potentially toxic materials, such as lead.

Nucleotide Excision Repair

This mechanism is used to replace regions of damaged DNA up to 30 bases in length. Common examples of DNA damage include ultraviolet (UV) light, which induces the formation of cyclobutane pyrimidine-pyrimi-dine dimers, and smoking, which causes formation of benzo pyrene-guanine adducts. Ionizing radiation, cancer chemotherapeutic agents, and a variety of chemicals found in the environment cause base modification, strand breaks, cross-linkage between bases on opposite strands or between DNA and protein, and numerous other defects. These are repaired by a process called nu-cleotide excision-repair (Figure 36-24). This complex process, which involves more gene products than the two other types of repair, essentially involves the hydrolysis of two phosphodiester bonds on the strand containing the defect. A special excision nuclease (exinuclease), consisting of at least three subunits in E coli and 16 polypep-tides in humans, accomplishes this task. In eukaryotic cells the enzymes cut...

Acquired mtDna Mutations

We have used two slightly different computational models to represent the somatic mutations that occur in mtDNA as part of the aging process. One method is to tie mutation to the replication process, to represent mutations that arise from replication errors. In this case, at every mtDNA replication event there is some probability Pmut that a new mtDNA mutation will be created. An alternative method is to model mutation formation independent of the mtDNA replication process. Then, over every time interval At there is a probability Pmut that a mtDNA molecule may be converted to a new mutation. Unless the replication rate is varying with time in the model, there is little significant difference between these two models for de novo mtDNA mutation formation. The parameter Pmut can also be made a function of time to represent changing mutation conditions, such as periods of increased radiation exposure, for example.

The Genetic Legacy of Chernobyl

Radiation is a known mutagen, causing damage to DNA. More than 13,000 children in the area surrounding Chernobyl were exposed to the radioactive isotope iodine-131 many had exposures 400 times the maximum annual radiation exposure recommended for workers in the nuclear industry. The rate of thyroid cancer among children in the Ukraine is now 10 times the pre-Chernobyl levels. Chromosome mutations have been detected in the cells of many people who resided near Chernobyl at the time of the accident, and birth defects in the population have increased significantly.

Pyrimidine dimers result from Ultraviolet light

Ionizing radiation also frequently results in double-strand breaks in DNA. Attempts to repair these breaks can produce chromosome mutations (discussed in Chapter 9). Ultraviolet light has less energy than that of ionizing radiation and does not eject electrons and cause ionization but is nevertheless highly mutagenic. Purine and pyrimidine bases readily absorb UV light, resulting in the formation of chemical bonds between adjacent pyrimidine molecules on the same strand of DNA and in the creation of structures called pyrimidine dimers (Figure 17.24a). Pyrimidine dimers consisting of two thymine bases (called thymine dimers) are most frequent, but cytosine dimers and thymine - cytosine dimers also can form. These dimers distort the configuration of DNA (Figure 17.24b) and often block replication. Most pyrimidine dimers are immediately repaired by mechanisms discussed later in this chapter, but some escape repair and inhibit replication and transcription.

Other Types of DNA Repair

The DNA repair pathways described so far respond to damage that is limited to one strand of a DNA molecule, leaving the other strand to be used as a template for the synthesis of new DNA during the repair process. Some types of DNA damage, however, affect both strands of the molecule and therefore pose a more severe challenge to the DNA repair machinery. Ionizing radiation frequently results in doublestrand breaks in DNA. The repair of double-strand breaks is frequently by homologous recombination. Models for homologous recombination were described in Chapter 12.

ATM and ATR Signalers of Genome Damage

A homozygous deficiency of ATM in humans leads to ataxia-telangiectasia (A-T), a debilitating disorder in which progressive loss of motor coordination (ataxia) is brought about by the gradual loss of Purkinje cells in the cerebellum 33 . In addition, A-T patients have an increased cancer incidence, and cells derived from these individuals are hypersensitive to ionizing radiation and to chemical agents that induce DNA double-strand breaks 33 . Notably, whereas normal cells delay progression through the cell cycle after treatment with such agents, A-T cells are defective in these checkpoint responses 5,6 . Indeed, A-T cells are deficient in the Gj S, G2 M, and S phase checkpoints. Over the past few years, a large number of research papers have addressed these checkpoint defects and it is now clearly established that ATM phosphorylates, and therefore appears to modulate the activities of, the key cell-cycle control proteins p53, BRCA1, NBS1, MDM2, RAD17, and CHK2. Recent review articles...

Conventional Methodologies

Comparison to the heart's total surface area. Thus, to obtain adequate electrical activity for activation patterns, it often dictates the placement of multiple catheters at numerous locations within the chamber of interest, which in turn requires a considerable amount of time this also leads to extensive use of fluo-roscopy, hence exposing the medical staff and patients to undesirable levels of ionizing radiation (15). Second, and perhaps more important, fluoroscopy does not sufficiently allow for the visualization of the complex 3D cardiac anatomy and or soft tissue characteristics of the heart's chambers (Fig. 1).

PIKK Family Members as Guardians of Nucleic Acid Structure Function and Integrity

It has been proposed that a common feature of the PIKK family may be an ability to interact with nucleic acids 41,42 . This is clearly established for DNA-PKcs, which stably binds to DNA upon interacting with DNA-bound Ku. Through this DNA-protein-protein interaction, the protein kinase potential of DNA-PK is released 4,25 . A role for DNA-PKcs in binding to telomeres has also been proposed 28 . In addition, ATM has been shown to bind in vitro to DNA with a preference for DNA termini or DNA that has been treated with ionizing radiation 43,44 . Also, within minutes of treating cells with ionizing radiation, ATM kinase activity is significantly increased 45,46 and the protein becomes associated with chromatin 47 . Likewise, stimulation of ATR activity by DNA in vitro has been observed 48,49 , suggesting a direct interaction with DNA or potentially an indirect interaction through its newly discovered partner ATRIP 50 . Indeed, recent work has revealed that the S. cerevisiae ATR ortholog,...

Applications of Magnetic Resonance Imaging to the Study of Development

Magnetic resonance imaging (MRI), with its lack of ionizing radiation and capacity to provide exquisite anatomical detail, has revolutionized the study of human brain development. Other imaging modalities, such as conventional radiography, computerized tomography (CT), positron emission tomography (PET), and single photon emission computerized tomography (SPECT), use ionizing radiation. Although these latter techniques may be used with pediatric patient populations when clinically warranted, the ethics of exposing children to radioactive isotopes for the advancement of science are less clear (Casey and Cohen, 1996 Morton, 1996 Za-metkin, 1996). The advent of functional MRI (fMRI) has further extended the utility of MRI to explore the developing human brain in ways not previously possible.

Types of Radiation Delivered

The radiation doses delivered to tumor and normal tissues during BNCT result from energy deposition from three types of directly ionizing radiation that differ in their LET characteristics (1) low-LET y rays, resulting primarily from the capture ofthermal neutrons by normal tissue hydrogen atoms 1H(n,Y)2H (2) high-LET protons, produced by the scattering of fast neutrons and from the capture of thermal neutrons by nitrogen atoms 10N(n,p)14C and (3) high-LET, heavier charged alpha particles (stripped down 4He nuclei) and lithium-7 ions. These are released as products of the thermal neutron capture and fission reactions with 10B 10B(n,a)7Li . The greater density of ionizations along tracks of high-LET particles results in an increased biological effect compared to the same physical dose of low-LET radiation. This usually is referred to as relative biological effectiveness (RBE), which is the ratio of the absorbed dose from a reference source of radiation (e.g., X-rays) to that of the...

Neoplastic Conditions

But can be associated with previous radiation exposure and Paget's disease. It is treated by a combination of chemotherapy and surgery. Ewing's sarcoma is a poorly differentiated, small, round, blue cell tumour seen in the long bones of children and young adults. It is treated with a combination of chemotherapy, radiotherapy and surgery. Chondrosarcomas are usually low-grade sarcomas occurring in long bones and flat bones in middle-aged and older people. They have a tendency for recurrence rather than metastasis. They do not respond to chemotherapy and treatment is surgical removal. The dedifferentiated chondrosarcoma is a high-grade tumour, typically large in size occurring in the pelvis and proximal femur of older people. These tumours metas-tasise early and have an extremely bad prognosis.

Introduction And Epidemiology

For the majority of patients in whom a meningioma develops, the etiology remains unclear 1-3,6,7 . Potential etiologic factors that have been investigated include radiation exposure, cranial trauma, viruses, hormonal stimulation, and molecular genetic events. The most consistently documented etiological factor appears to be prior cranial radiation exposure. Meningiomas have been shown to be induced by low- and high-dose irradiation 6,7,9,10 . To meet the criteria for a radiation-induced tumor, the mass must occur within the irradiated field, develop after a period of latency following irradiation (e.g., 20-30 years), and be histologically different from any preexisting neoplasm in the region. Children treated with

Diagnostic Investigation

Although the basic diagnostic approach to thromboembolism is the same in pregnant and non-pregnant women, concern about radiation exposure and the normal anatomical changes seen in pregnant women add complexity to the diagnostic algorithm. Leg studies for PE One way to avoid radiation exposure in the setting of pregnancy is to perform non-invasive leg studies. This is prudent even in cases of a suspected pulmonary embolism since deep venous thrombosis will be present in 30-70 of women with proven pulmonary embolism. If deep venous thrombosis is present, this establishes the need for anticoagulant therapy and negates the need for further studies.

Effects of Oxidative Stress and Genotoxic Stress on Zebrafish Aging and Senescence

Several lines of evidence suggest that genotoxic or oxidative stress promote the aging process (Campisi, 2005 Finkel and Holbrook, 2000 Lombard et al., 2005). It is well known that the aging process diminishes the capability to adapt to environmental stresses. We hypothesized that genotoxic and oxidative stress leads to mutations and general declines in reproductive ability, ultimately producing the spectrum of age-related characteristics in zebrafish. Support for this idea comes from the fact that radiation increases genetic mutations and leads to premature aging in animals, such as mice and Medaka fish (Oryzias latipes) (Curtis, 1963 Egami and Eto, 1973 Ferbeyre and Lowe, 2002 Trifunovic et al., 2004 Tyner et al., 2002 Celeste et al., 2002). Therefore, we have subjected embryos and adult zebrafish to genotoxic or oxidative stress and measured aging markers over the lifespan of the fish. To determine the effects of genotoxic and oxidative stresses on zebrafish aging, we have analyzed...

Protection of the Examining Physician

Mri Cable Burns

Most factors that serve the radiation protection of the patient also diminish the radiation exposure of the radiologist. These include the adequate experience of the examining physician, short fluoroscopy times, strict collimation of the x-ray beam, dose-minimized x-ray equipment, and a strict adherence to the indication list. One very effective protective measure is to keep the greatest possible distance (dose decreases by the square of the distance) from the primary or secondary sources of radiation (the tube and the patient). Another measure is to protect the physician with lead-lined, sometimes movable, walls, lead aprons, gloves, thyroid protectors, and awkward-looking lead-glass goggles or spectacles (Fig. 5.3). Further risks to human life and health due to the commonly used MR techniques are not known. Elective MR studies of women in early pregnancy (up to the third month) are nonetheless discouraged because of residual safety concerns. In vital indications in this patient...

Overview Of Biomarkers

Cytogenetic biomarkers currently applied in molecular epidemiological studies include chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN). Chromosome aberrations are structural alterations, breaks, and rearrangements in chromosomes. Recently developed analytic methods using fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) provide detection of new types of rearrangements and translocations of specific regions in certain chromosomes (39, 40). Exposure to ionizing radiation, alkylating cytostatics, tobacco smoking, benzene, and styrene has been found to induce CAs in humans (18). Sister chromatid exchange represent symmetrical exchanges of DNA segments between the sister chromatids of a duplicated metaphase chromosome. Tobacco smoking, alkylating cytostatics, and ethylene oxide can induce SCEs in human lymphocytes (41). Micronuclei are small additional nuclei observable in interphase cells. Increased MN frequencies in human...

Angiogenesis Basic Mechanisms and Role in Head and Neck Squamous Cell Carcinoma

The vast majority (95 ) of head and neck tumors are squamous cell carcinomas (HNSCC), the most common type of cancer affecting the lining of the airways and upper digestive organs. HNSCC comprises a wide variety of epithelial malignant lesions affecting the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, lips, alveolar ridge and retromolar trigone, floor of the mouth, tongue, hard and soft palat, tonsil, pharyngeal wall, larynx, hypopharynx, and salivary glands. Cancer in these locations originates from the cuboidal cells along the basement membrane of the mucosa and usually has profound impairing effects on breathing, speaking, and swallowing. The disease is characterized by local tumor aggressiveness, early recurrence, and high frequency of second primary tumors. Neoplasias of the head and neck region are relatively infrequent in comparison with cancer occurring in the breast, lung, prostate, and colon and represent approximately 5.6 of all tumors....

Maintaining Spice Quality

Irradiation, first approved by FDA for use on spices in 1983, exposes spices up to a million rads of ionizing radiation, the highest amounts allowed for any food. Approved by ASTA, this process more effectively kills microbes than EtO. Concerns have been expressed by EPA that irradiation changes the chemical composition of a spice, potentially creating toxic and carcinogenic by-products in the food. This method is banned in Japan. It also reduces the sensory and nutritional quality of the spices and gives a lower consumer acceptance.

Inflammatory Autoimmune

Radiation therapy, with or without chemotherapy, has become the primary treatment for oropharyngeal cancer. Primary treatment of head and neck neoplasms with radiation most commonly ranges from 60 to 70 Gy. Radiation exposure greater than 5 Gy may induce some degree of acute and or chronic pharyngitis in nearly all

Experimental Results and Comparison

The imaging justification for blending is readily apparent a cancer is visible in a mammogram because of its (slightly) higher X-ray attenuation, which causes a lower radiation exposure on the film in the appropriate region of a projected image.

Therapeutic Implications

Several lines of investigation identify PI3-kinase as a regulator of cellular responses to ionizing radiation. Biochemical inhibitors of PI3-kinase, LY294002, and wortmannin, enhance the anti-neoplastic effects of radiation 64-66 , and recent data indicate that PKB Akt mediates LY294002-mediated radiosensitization 82 . Ionizing radiation has been shown to activate PKB Akt and p70S6K in epithelial tumors in vitro, however this has not been shown to be the case in malignant glioma cell lines (Nakamura and Haas-Kogan, unpublished data). In addition to direct effects on tumor cells, PKB Akt mediates responses of vascular endothelium to ionizing radiation 67 . PI3-kinase inhibition may provide a means of targeting elements in the tumor microenvironment such as vascular endothelium 68 . Thus, PI3-kinase inhibition may have anti-neoplastic effects through direct tumor killing as well as through disruption of the supportive microenvironmental components such as vascularization 69 . 67. Zingg,...

Health Policies and the Physical Environment

When people are exposed to harmful agents such as asbestos, dioxin, excessive noise, ionizing radiation, or toxic chemical and biological agents, their health is directly affected. Dangerous exposure possibilities pervade the physical environments of many people. Some of the exposure is through such agents as synthetic compounds that are introduced into the environment as by-products of technological growth and development. Some exposure is through wastes that result from the manufacture, use, and disposal of a vast range of products. And some of the exposure is through naturally occurring agents such as carcinogenic ultraviolet radiation from the sun or naturally occurring radon gas in the soil.

Risk Factors

Research into the etiology and possible contributing causes of gliomas is ongoing, but is hindered by many factors including the relative rarity of the disease and rapid death of patients with aggressive subtypes. As such, studies to date have revealed little with regard to specific causal factors. High-dose therapeutic ionizing radiation to the head, administered for benign conditions or for cancer treatment, has been shown to increase the risk of glioma as well as meningioma and nerve sheath tumors (9).

Ultrasonography

US is universally the most widely available imaging modality for screening of liver masses or obstructive jaundice. It is noninvasive, quick, portable, and relatively inexpensive, and it uses no ionizing radiation. The most significant advances in abdominal US are harmonic imaging and the use of intravenous contrast agents to characterize and detect lesions in the liver (Leifer et al, 2000). Analysis of image quality has shown that sonograms obtained with the harmonic imaging technique are significantly better than those obtained with the conventional B-mode technique, and most investigators have recommended routine use of harmonic imaging for abdominal US studies, especially in adult patients. In experienced hands, US can accurately distinguish a benign or insignificant lesion, such as a cyst or cavernous hemangioma, from a malignant lesion, such as a hepatic metastasis or a hepatocellular carcinoma (Wilson et al, 2000). Harmonic imaging has significantly enhanced the uses of...

Nuclear Agents

A Radiation Dispersal Device is more commonly known as the dirty bomb. A dirty bomb combines a conventional explosive, such as dynamite, with radioactive material. The conventional explosive itself would cause more casualties than the radioactive material. At the levels created by most probable sources, not enough radiation would be present in a dirty bomb to kill people or cause severe illness. However, the detection of radiation after an overt terrorist attack would lead to the development of panic and probably require decontamination or evacuation of the affected urban area with considerable disruption. A second use would be to hide a strong radiation source in a public place, exposing persons to radiation until it was detected. For further details, please chapter 40 on Nuclear Detonation Ionizing Radiation Exposure.

Diagnosis

The main imaging techniques (MRI, CT, DEXA) differentiate tissues on the basis of density. Single-slice measurements of the abdomen and extremities (subcutaneous adipose tissue SAT, visceral adipose tissue VAT) and more complex three-dimensional reconstructions have been used to calculate regional or total body fat. Limitations of these methods include most notably their expense, availability and radiation exposure (CT). Consequently, CT and MRI should only be considered in routine clinical practice for selected patients (e.g. extended dorso-cervical fat pads, differential diagnosis of non-benign processes and infections).

Summary

Technology has provided us with both a safer, more nutritious food supply and purified water sources. Tampering or malfunction of these processes may alter their quality with the potential for widespread outbreak of food-borne or waterborne disease. Care of these patients should focus on hydration and antibiotic therapy in certain instances. Trichothecene mycotoxicoses may be of natural or artificial origin with a clinical presentation consistent with vesicant or radiation exposure. Treatment for these cases is supportive. Decontamination of equipment status post any food or waterborne outbreak requires special attention.

Dose Escalation

There has been significant interest in the use of halogenated pyrimidines, bromodeoxyuridine (BudR) and iododeoxyuridine (IudR) as radiosensitizers. The incorporation ofthese compounds into DNA of rapidly dividing cells weakens the DNA structure and makes it mores susceptible to ionizing radiation. Gliomas represent an ideal target for the study of such radiosensitizers because highly proliferating tumor cells are surrounded by nonproliferating normal brain tissue that shows little to no DNA incorporation of the halogenated pyrimidines. Radiosensitizers are only effective in cells that take up the Brachytherapy. Brachytherapy involves insertion of permanent or temporary radioactive sources within tumor harboring tissues. One of the advantages of brachytherapy is the rapid reduction in dose that allows higher doses to be delivered to high-risk areas while minimizing radiation exposure to surrounding normal tissues. It has been used as a method for dose...

Hazard Types

Radiation exposure limits for members of the general public have been determined by federal regulatory agencies and radiation protection consensus groups (4,5). Individuals who are infrequently exposed to sources of radiation, for example, funeral home directors, are allowed to receive 100 mrem whole body annually. Individuals who are frequently exposed may receive 500 mrem whole body annually. Hands are relatively insensitive to radiation and therefore have a recommended annual limit of 5,000 mrem.

General Precautions

Reducing time, increasing distance, and using shields are methods to reduce radiation exposure. Keeping the time of exposure at a minimum is the principal method of dose reduction for autopsy personnel. Extremity distance can be achieved through the use of long-handled instruments. Shielding with a radiology lead apron (0.5 mm lead equivalent thickness) would provide some protection for gamma radiation from 99mTc and 125I but would do little for highly penetrating gamma rays from 103Pd, 131I, 182Ta, and 198Au. Common barrier protection as determined by consensus standards (6) includes numerous items that minimize external radiation exposure from beta-emitting radioisotopes (when body cavities are opened) and assist in the prevention of personal contamination. These include double-gloves, hair covers, long-sleeved jump suits that are fluid resistant, foot covers, and facial protection (splash guards). Any wound sustained during procedures on a radioactive body should be attended...

Autopsy

Precautions designed to reduce radiation exposure of employees included the use of personal protective equipment, limiting personnel time (20-min rotations), instructing staff to maintain increased distance from the cadaver when feasible, and general methods to reduce room contamination. When this was tested, employees other than the lead pathologist received a maximum of 13 mrem to the whole body and 59 mrem to the hand (9). Radiation Exposure Rates From Radioactive Implants Radiation Exposure Rates From Radioactive Implants

Endometriosis

Endometriosis in captive colonies of female rhesus monkeys can occur in relatively high incidence ( 26 ). The causes of endometriosis appear to be varied and range from surgery to radiation exposure (Fanton and Golden, 1991). One of the major issues of endometriosis, especially in rhesus macaques, is diagnosis at a treatable stage of the disease. As observed by a number of laboratories, endometriosis is difficult to diagnose until relatively advanced (Rippy et al., 1996). Use of indicators, such as plasma levels of CA-125, have been examined as a possible indicator of endometriosis (Rippy et al., 1996). The condition is accompanied by lesions, cyst formation, adhesions to organs, anorexia, and abdominal masses

Leukemias

Most cases of leukemia are sporadic with no identifiable cause. Certainly, exposure to ionizing radiation and other carcinogens such as certain chemotherapeutic agents can be implicated in some cases. Many recurring genetic lesions have been described that result in the disruption of normal regulatory pathways. Autonomous proliferation may occur as a result of activating mutations. Increased self-renewal, loss of cell-cycle control, escape from apoptosis, and a block of cellular differentiation have all been reported (8). Acute promyelocytic leukemia (AML M3), which frequently presents with a low white blood cell (WBC) count and evidence, either laboratory, clinical, or both, of disseminated intravascular coagulation (DIC), is associated with the t(15 17) in most cases. The resulting fusion transcript promyelocytic leukemia-retioic acid receptor alpha (PML-RARa) predicts responsiveness to all-trans retinoic acid (ATRA), which has been used along with chemotherapy to manage this...

Energy therapies

Energy therapies is a collective term used to refer to a variety of alternative and complementary treatments based on the use, modification, or manipulation of energy fields. Most energy therapies presuppose or accept the theory that matter and energy are not exclusive opposites, but that matter is simply a denser form of energy that is more easily perceived by the senses. Some energy therapies are associated with systems of traditional Indian or Chinese medicine that are thousands of years old others draw upon contemporary scientific theories. Energy therapies can be divided for purposes of discussion into two groups those that utilize energy fields located in, affecting, or emanating from the human body (biofield therapies) and those that use electromagnetic fields in unconventional ways. In addition, there are energy therapies that combine biofield therapy with some aspects of bodywork Breema, polarity therapy, and qigong are examples of this combined approach.

HERKinase EGFR Axis

Radiation exposure causes phosphorylation and activation of EGFR as if by ligand, which results in activation of downstream kinases that inhibit apoptotic response (e.g., MAPK, Akt). In addition, Rao and colleagues have shown that transfection of human glioma cell lines with dominant negative EGFR mutants causes radiosensitization (4). Inhibition of EGFR by C225 anti-EGFR MAb or by CI-1033 tyrosine kinase inhibitor also sensitizes cells to radiation (4).

Radiation

In 1927, Herman Muller demonstrated that mutations in fruit flies could be induced by X-rays. The results of subsequent studies showed that X-rays greatly increase mutation rates in all organisms. The high energies of X-rays, gamma rays, and cosmic rays (< Figure 17.23) are all capable of penetrating tissues and damaging DNA. These forms of radiation, called ionizing radiation, dislodge electrons from the atoms that they encounter, changing stable molecules into free radicals and reactive ions, which then alter the structures of bases and break phosphodiester 17.23 In the electromagnetic spectrum, as wavelength decreases, energy increases. (Adapted from Life 6e, figure 8.5).

Cancer

Mutations and DNA damage are not only the result of exposure to exogenous carcinogens. Endogenous DNA-damaging agents result in a background level of damage (6-8). Table 2 gives some examples. The endogenous part can be subdivided into chemical and biochemical processes, and it includes the consequences of oxygen stress. The exogenous sources have been subdivided according to the question of avoidability rather than type. Numerous exogenous sources can hardly be eliminated. Physical carcinogens, such as UV and ionizing radiation, have for a long time been accepted to result in a background DNA damage. Accordingly, exposure standards at the workplace have been set in relation to a background dose. For chemical carcinogens, this has not been done. The idea prevailed that chemically induced DNA damage could be avoided if it were possible to exclude exposure to exogenous carcinogens. On this basis, exposure standards for exogenous genotoxic carcinogens were often set to 0 (i.e., the...

Causes of stress

One significant source of stress in modern life is the cumulative effect of various toxic waste products on the environment. Studies of the aftermath of such environmental disasters as Three Mile Island and Chernobyl found that not only evacuees and people living in the contaminated area had high levels of emotional distress, but also cleanup workers and people living in nearby noncontaminated areas. In the case of Chernobyl, Russian physicians have reported a psychoneurological syndrome with several unexplained symptoms, including fatigue, impaired memory, muscle or joint pain, and sleep disturbances. The syndrome appears to be due to chronic emotional stress rather than radiation exposure.

Intraoperative Ct

Digital imaging in the neurosurgical OR was first done using CT, where a dedicated unit was installed at the University of Pittsburgh 11 . In general, CT scanners are less expensive than MRI units, but acceptance of this technology has been limited by several factors. These include the lower soft tissue contrast compared to MRI, bone hardening artifact in the posterior fossa, the use of ionizing radiation, and likely need for a dedicated technologist to operate the system. Nonetheless, the rapid scan times and the potential applications for spine surgery make iCT potentially useful, and investigators have continued to evaluate its use 12 .

Ultrasound

Still, a useful iUS system is attractive because it has a lower price tag than iMRI or iCT. Also, ionizing radiation would not be used, and room shielding or instrument modification would not be needed. As a result, investigation of iUS imaging and navigation technology continues 14 .

Coalescence

In addition to the inherent processes that destabilize emulsions, other factors may be involved. Storage temperature has been shown to affect emulsion product stability. Generally, elevated temperatures result in destabilization, while reduced temperatures improve emulsion stability. Aqueous-phase evaporation may also contribute to instability over the life of a product. Microbial contamination can also cause a breakdown of emulsion stability. Finally, chemical reactions within the emulsion can lead to a change in the stability of the emulsion. While these types of reactions can be initiated by temperature increases, they can also be prompted by UV light or other types of electromagnetic radiation.

Pathophysiology

Family history of breast cancer in a first degree relative and history of benign breast disease also increase the risk of breast cancer. The use of estrogen replacement therapy or oral contraceptives slightly increases the risk of breast cancer. Radiation exposure and alcoholic beverage consumption also increase the risk of breast cancer.

Mutagens

Since mutations occur in the natural process of DNA replication, how shall we define mutagens It would be strange to define the natural replication of DNA as mutagenic. Thus we will define mutagens as factors that increase the rate of mutation over and above that of the spontaneous mutation rate. Two categories of mutagens will be discussed. One is electromagnetic radiation and the other comprises various chemicals. First, let us look at electromagnetic radiation. Electromagnetic radiation ranges from radio waves to X rays and gamma rays. Our eyes see just a small portion of this spectrum, the visible wavelengths of light. Microwaves are used in microwave ovens, while infrared radiation can be thought of as heat waves. These two types of electromagnetic radiation are not mutagenic. Electromagnetic waves shorter than visible light, including UV, or ultraviolet rays, gamma rays, and X rays are mutagenic they increase the mutation rate above the spontaneous rate.

Concepts Summary

Ionizing radiation is mutagenic, altering base structures and breaking phosphodiester bonds. Ultraviolet light produces pyrimidine dimers, which block replication. Bacteria use the SOS response to overcome replication blocks produced by pyrimidine dimers and other lesions in DNA, but the SOS response causes the occurrence of more replication errors. Pyrimidine dimers in eukaryotic cells can be bypassed by DNA polymerase but may result in the placement of incorrect bases opposite the dimer.