Role of induced genetic instability in the mutagenic effects of chemicals and radiation.
Recent studies have demonstrated that cells exposed to ionizing radiation or alkylating agents can develop prolonged genetic instability. Induced genetic instability is manifested in multiple ways, including delayed reproductive death, an increased rate of point mutations, and an increased rate of chromosome rearrangements. In many respects these changes are similar to the genetic instability associated with cancer and some human genetic diseases. Therefore, as with cancer cells, multiple mechanisms may be involved, some occurring in the early stages and some in the later stages. The high percentage of cells that develop induced genetic instability after exposure to stress, and the prolonged period over which the instability occurs, indicates that the instability is not in response to residual damage in the DNA or mutations in specific genes. Instead, changes affecting most of the exposed cells, such as epigenetic alterations in gene expression or chain reactions of chromosome rearrangements, are a more likely explanation. Learning more about the mechanisms involved in this process is essential for understanding the consequences of exposure of cells to ionizing radiation or alkylating agents.
Murnane
J P
JP
Laboratory of Radiology and Environmental Health, University of California, San Francisco 94143-0750 USA.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002869:Chromosome Aberrations; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens; D009369:Neoplasms / Q000235:genetics; D017354:Point Mutation; D011839:Radiation, Ionizing
D000477:Alkylating Agents; D009153:Mutagens