Mutagens

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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.

For example, we know that UV light causes specific damage to DNA in the form of thymine dimers. These occur when two Ts adjacent to each other in a DNA molecule fuse together under the effect of UV light. Thymine dimers deform the DNA double helix and greatly increase the possibility of errors in DNA copying. Our cells possess two different repair mechanisms to minimize errors due to thymine dimers. Individuals with defects in either of these repair mechanisms are highly sensitive to UV radiation and are prone to skin cancer. Understandably, there is much concern about increased exposure to UV rays. For example, recent studies show that people using tanning salons increase their chances of getting skin cancer. The shrinking ozone layer is a related concern because ozone helps to prevent harmful UV rays from reaching the surface of the earth. As this ozone layer becomes depleted, we may expect mutation rates to increase in many organisms.

X rays, such as those used in medical diagnosis, are also mutagenic. Patients exposed to X rays use protective lead shields on parts of the body that are not being X-rayed to minimize exposure to the mutagenic effect of X rays. For example, women getting mammograms must be careful to shield their reproductive organs.

Radioactive materials, natural or manmade, are mutagenic as well. All living things that were exposed to radioactive fallout from atomic bomb testing, the atomic bombs dropped on Hiroshima and Nagasaki in 1945, or from nuclear power plant accidents such as Chernobyl (in Ukraine) in 1986, experienced increased mutations if they survived. It is estimated that over 3.5 million people were contaminated with radioactive fallout from the Chernobyl accident. Many different radioactive compounds were released in these and other accidents, but of greatest concern to people is radioactive iodine, 131I. Radioactive iodine is particularly dangerous because the human body accumulates it in the thyroid gland. In fact, a sharp increase in thyroid cancer among children in Ukraine and Belarus was detected four years after the Chernobyl accident, with some areas having thirty to one hundred times the expected rate of thyroid cancers. There are compa nies selling iodine pills in the form of potassium iodide (KI) that one can take to block the uptake of radioactive iodine that might be accidentally released. Some public agencies are urged to keep a stock of iodine pills in case of emergency.

Chemicals can also be mutagenic, either because they directly damage DNA or because they may be similar in structure to a nucleotide and so can fool the cellular machinery responsible for DNA replication. A chemical in the first category is nitrous acid. We do not eat nitrous acid, but chemicals that are often used in food processing, nitrates and nitrites, are converted into nitrous acid by the acid in our stomach. Once nitrous acid is made in this way, it can convert a C to a U. U is normally only found in RNA, but when it is formed by nitrous acid in the DNA, a G-C base pair is converted into a G-U base pair. When this mutated DNA is replicated, one strand will still have a G-C pair and is normal. However, the base pair in the other strand is made into a U-A pair because U is similar to T. The result of the nitrous acid damage then is to convert a G-C base pair to a T-A base pair. A chemical in the second category is caffeine, the stimulant in coffee and cola drinks. Caffeine's structure is similar to that of a nucleotide, but it is not exactly the same. Thus, when caffeine is incorporated into the structure of DNA, its base sequence can become altered after replication.

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