RELATION BETWEEN DNA REPAIR, CHROMOSOME ABERRATIONS, AND SISTER CHROMATID EXCHANGES

Abstract

ABSTRACT Ordinary chromosome aberrations and sister chromatid exchanges (SCEs), which are two types of cytogenetic endpoints that are currently being used to determine the effects of mutagens and carcinogens on chromosomes, differ in several aspects. A) Double stranded DNA breaks, which are induced by X Rays, lead to aberrations but not to SCEs. B) Ordinary chromosome aberrations that are induced by ultraviolet light are photoreactivable, whereas we now have found in chick embryo cells that even though thymine dimers are removed by PR light, the yield of UV-induced SCEs is unaffected. C) Aberrations induced by UV or “UV-like,” but not “X-ray-like” mutagens are higher in XP cells than in normal cells, whereas SCEs are higher in XP cells after treatment with all three types of mutagens. D) The aberration yields are related to the amount of excision repair as measured by unscheduled DNA synthesis or repair replication whereas SCE yields are not. E) Aberrations are increased by application of caffeine after treatment with UV light or chemical mutagens but SCEs are not, and in post-replication defective XP variant cells, UV-induced SCE levels are as in normal cells. Taken as a whole these data indicate that although aberrations are dependent upon excision repair and post-replication repair as measured in ordinary experiments, SCEs are not. The lesions that result in SCEs do not seem to be thymine dimers or alkylation products at the N 7 position of guanine. Since SCEs are induced by long-lived lesions that disappear with time, minor photoproducts, or alkylation products, that are not measured in excision repair or post-replication repair experiments seem to be the lesions responsible for SCE formation, which is contrary to the findings for chromosome aberrations.