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Relationships between Mutagen-induced DNA repair, chromosome aberrations and sister chromatid exchanges MacRae, W. Donald


The induction of sister chromatid exchanges(SCEs) and chromosome aberrations by mutagenic agents was examined in normal human and xeroderma pigmentosum cells and Chinese hamster ovary (CHO) cells. The effects of the alteration of 5'-bromodeoxyuridine concentration on the spontaneous and mutagen-induced SCE frequency, the time of treatment and sampling, and the duration of mutagen treatment were each considered with respect to the applicability of the technique, as a test for detecting mutagenic and carcinogenic agents. SCE induction by U.V. light,4-nitroquinoline 1-oxide and N-methyl-N'-nitro-nitrosoguanidine in xeroderma pigmentosum and normal human cells was studied as a possible means of examining the relationships between unscheduled DNA synthesis, chromosome aberrations and SCEs. Xeroderma pigmentosum cells were more responsive than normal cells with respect to SCE formation after treatment with each of these mutagenic agents. To further probe the relationships between SCEs, chromosome aberrations, DNA repair and cell survival, the response of cells arrested by amino-acid deprivation to mutagen treatment was examined. CHO cells were arrested by arginine deprivation and treated with mutagen. They were found to be markedly more sensitive than dividing cells, showing a reduced survival and an elevated frequency of chromosome aberrations. No removal of those lesions which produced chromosome aberrations was detected after post-treatment incubation in arginine deficient medium. U.V.-induced SCEs, on the other hand, could be reduced in number by holding the cells in arginine deficient medium for 24 hours after irradiation. This phenomenon, which was interpreted as the removal of SCE-producing lesions, was not observed after treatment with either of the alkylating agents N-methyl-N'-nitro-nitrosoguanidine or mitomycin C. The implications of these findings with respect to mammalian DNA repair mechanisms are discussed.

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