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Genetics 301 Lecture #16
Spring 2003, March 11, 2003

Induced mutations can result from chemical or radiation treatments. In addition to chemicals which can substitute for normal bases (base analogs) and chemicals which modigy bases, some chemicals can intercalate between adjoining bases. Many dyes behave in this manner. The result is insertions or deletions, leading to frameshift mutations.

Radiation treatments include UV light and ionizing radiation. UV light exposure is a major source of skin cancer. Mutations are associated with the formation of pyrimidine dimers. Individuals with xeroderma pigmentosum are highly susceptible to UV damage since they do not repair it effectively. The decay of the ozone layer due to CFCs (chlorofluorocarbons) is leading to more penetration of UV light.

Ionizing radiation is also a concern. Examples include X-rays and gamma rays. Ionizing radiation reacts with water to lead to production of "free radicals" which can damage DNA through strand breaks. Damage increases in a linear fashion with dose. Damage to people can lead to cancer and to increased mutation. After Hiroshima and Nagasaki, cancer incidence increased but there was not evidence for germline mutations being passed on at increased frequency. At Chernobyl, cancer was increased and there was also an increased rate of germ line mutation in STRPs (simple tandem repeat polymorphisms) was detected.

DNA repair is ongoing in cells and important in relation to cancer. Types include: excision repair, mismatch repair, photoreactivation and postreplication repair.

The Ames test relies on reversion of His — to His + Salmonella bacteria to detect the genetic damage caused by some chemicals. An increased incidence of His + colonies in the presence of a chemical indicates that a chemical is mutagenic. The Ames test has been modified to allow testing of chemicals which are activated into a mutagenic form inside the animal In this type of test, His — Salmonella may revert into His + in the presence of minimal medium, the chemical plus rat liver extract. Different types of His — strains have been developed with different types of mutations (e.g., base substitution, frameshift). Different chemicals may have different abilities to cause reversion of these mutations. Most potential carcinogens can be detected using the Ames test. In many cases results from this test may be tested further through cancer studies in mice or rats.

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