Application Of Biomarkers For Human Risk Assessment

Many studies have used DNA and protein adducts to assess potential sources of environmental carcinogen exposure. One important study examined a variety of molecular biomarkers to assess human exposure to complex mixtures of environmental pollution in Poland (125). Measurement of genotoxic damage in peripheral blood samples from residents of high-exposure regions indicated that environmental pollution was associated with significant increases in carcinogen-DNA adducts (polynuclear aromatic...

Uses And Interpretation Of Data

The uses of the in vitro micronucleus assay are too numerous to review, but recent examples are described briefly, below. One major use of the assay, not discussed here because it is beyond the scope of this chapter, is in assessing environmental and occupationally induced chromosome damage in vivo in humans. A. Chemical-Specific Investigations The in vitro micronucleus assay is used to study the genotoxicity of specific chemicals of interest. These type of studies often use the standard...

B DNA Tumor Viruses

Just as RNA tumor viruses helped to elucidate the role of oncogenes, DNA tumor viruses have served to highlight the role of TSGs. Exposure of cells to a DNA virus may result in a productive infection and a subsequent lytic cycle, or it may transform the cell randomly, integrating its own genome into host chromosomes. When cells are transformed, they lose contact inhibition, require less serum, and grow to a high cell density, producing multilayered colonies. When grown in semisolid agar, they...

The Two Stage Clonal Expansion Model

The two-stage clonal expansion model (10, 11, 27) posits that malignant transformation of a susceptible cell is the result of two specific, rate-limiting, hereditary (at the level of the cell), and irreversible events. I emphasize that this model should not be interpreted as positing that carcinogenesis results from two specific locus mutations. Rather, this model is best interpreted within the initiationpromotion-progression paradigm of chemical carcinogenesis. Initiation, which confers a...

Cancer

Schematic representation of the multimutational process of carcinogenesis. Individual factors (in italics) modulate the rate of the process or affect the number of steps required for malignant transformation. (From Ref. 4, with permission of Elsevier Science.) damage but also by damage associated with misrepair, DNA replication, and chromosome segregation. The most direct type of DNA damage is a chemical interaction of the chemical with the DNA molecule, for instance, by covalent...

References

Mechanisms of carcinogenesis and biologically based models for estimation and prediction of risk. In S Moolgavkar, D Krewski, L Zeise, E Cardis, H Moller, eds. Quantitative Estimation and Prediction of Human Cancer Risk. Lyon IARC Scientific Publications, No. 131, 1999, pp 179-237. 2. H Vainio, PM Magee, DB McGregor, AJ McMichael. Mechanisms of Carcinogenesis in Risk Identification. Lyon IARC Scientific Publications, No. 116, 1992. 3. KS Crump, DG Hoel, CH...

Kidney Cancer in Male Rats and a2Microglobulin Nephropathy

Alpha(a)-2-microglobulin (a-2mG) associated nephropathy has been evaluated as a mechanism of renal tubular cell carcinogenesis in male rats (16-18). The hypothesis supporting this mechanism is based on the finding that chemicals that induce a-2mG accumulation and renal carcinogenesis in male rats have not been shown to induce kidney tumors in animals that lack the ability to synthesize a-2mG in the liver. However, both data that are consistent and inconsistent with this hypothesis exist (16)....

Overview Of Biomarkers

As adapted from a report by the Committee on Biological Markers of the National Research Council (6), the development of disease that results from exposure to an environmental agent or other toxicant is multistage, starting with exposure, progressing to internal dose (e.g., deposited body dose), to biologically effective dose (e.g., dose at the site of toxic action), to early biological effect (e.g., at the subcellular level), to altered structure or function (e.g., subclinical changes), and...