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DNA ALTERATIONS
Citation:
Shugart, L., J. Bickham, G. Jackim, G. McMahon, W. Ridley, J. Stein, AND S. Steinert. DNA ALTERATIONS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/A-93/164 (NTIS PB93221828), 1992.
Description:
The exposure of an organism to genotoxic chemicals may induce a cascade of genetic events. nitially, structural alterations to DNA are formed. ext, the DNA damage is processed and subsequently expressed in mutant gene products. inally, diseases result from the genetic damage. he detection and quantitation of various events in this sequence may be employed as biomarkers of exposure and effects in organisms exposed to genotoxic agents in the environment. he methods to monitor exposure to genotoxic chemicals are based upon either (1) direct measurement of DNA structural change; (2) the detection of their consequences by measuring DNA repair directly or indirectly; or (3) the production of mutations in the genome of the exposed organisms. dducts are a type of structural change involving covalent attachments of a chemical or its metabolite to DNA. everal analytical procedures are currently used to monitor the formation of DNA adducts directly; the most prominent of these procedures is the 32P-postlabeling technique. ore general approach involves the detection of DNA breaks that are produced either directly by the toxic chemical or by the processing of structural damage. he detection of this type of damage is facilitated by the alkaline unwinding assay. he current methods available for monitoring the consequences of DNA damage are based upon changes to chromosomes, such as aberrations, formation of micronuclei, detection of abnormal distribution of DNA within cells, and the activation of proto-oncogenes. he activation of oncogenes and inactivation of tumor suppressor genes are areas of research that should receive greater emphasis in the future.