期刊
CARCINOGENESIS
卷 21, 期 9, 页码 1639-1646出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/21.9.1639
关键词
-
类别
资金
- NCI NIH HHS [CA48066, CA21253] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA048066, R01CA021253] Funding Source: NIH RePORTER
O-6-methylguanine is responsible for homologous recombination induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [H.Zhang et al, (1996) Carcinogenesis, 17, 2229], To test the hypothesis that mismatch repair is causally involved in this process, we generated mismatch repair-deficient strains from a human fibroblast line containing a substrate for detecting intrachromosomal homologous recombination, The four strains selected for study exhibited greatly increased resistance to the cytotoxic effects of MNNG, which was not affected by depletion of O-6-alkylguanine-DNA alkyltransferase, and greatly increased sensitivity to the mutagenic effect of MNNG, suggesting that the mutagenic base modifications induced in these four cell strains by MNNG persist in their genomic DNA, Tests showed that their extracts are deficient in the repair of G:T mismatches. The frequency of homologous recombination induced by MNNG in three of these strains was significantly (5-7-fold) lower than that induced in the parental cell strain. This was not the result of a generalized defect in recombination, because when (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was used to induce recombination, all three lines responded with a normal or even a somewhat higher frequency than that observed in the parental strain. The lack of recombination displayed by the fourth strain was shown to result from the loss of part of the recombination substrate. The results strongly suggest that functional mismatch repair is required for MNNG-induced homologous recombination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据