The induction of SCE with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-N-nitrosourea and dimethylsulfate.
The relationship between the formation of alkylated purines in DNA and sister chromatid exchange (SCE) induction has been studied. Both exponentially growing and density-inhibited Chinese hamster (V79) cultures were treated with various doses of N-methyl-N-nitrosourea (MNU) or dimethylsulfate (DMS). The colony-forming ability and induced frequencies of SCEs were assayed. Following the exposure of density-inhibited cells to radiolabeled methylating agents these phenomena were related to the levels of 7-methylguanine (7-meGua), 0(6)-methylguanine (0(6)-meGua) and 3-methyladenine (3-meAde) in the DNA. At equitoxic doses MNU and DMS induced similar frequencies of SCEs. Since, at equitoxic doses MNU produces about 20 times more 0(6)-meGua in V79-cell DNA than does DMS, this indicates that the formation of this adduct in DNA is not critical for the induction of SCEs by these alkylating agents. Dimethylsulfate-induced SCEs may be mediated via the production of both 3-meAde and 7-meGua in the DNA; these 2 methylated purines may also be responsible for MNU-induced SCE. No one specific methylated purine was identified, therefore, as being solely accountable for the formation of SCEs. The repair of lesions in the DNA of nonreplicating V79 cells lead to a reduction in the SCE frequency on their subsequent release from the density-inhibited state. This suggests that excision repair is not responsible for the formation of SCEs.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D008168:Lung; D008297:Male; D008745:Methylation; D008770:Methylnitrosourea / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011687:Purines / Q000032:analysis; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D013464:Sulfuric Acids / Q000494:pharmacology*
D009607:Nitrosourea Compounds; D011687:Purines; D013463:Sulfuric Acid Esters; D013464:Sulfuric Acids; D008770:Methylnitrosourea; D004247:DNA; C007482:dimethyl sulfate