DNA-protein cross-linking by chemical carcinogens in mammalian cells.
The induction of DNA cross-linking in mammalian cells by various carcinogens was investigated by the method of alkaline elution. A dose-dependent increase in DNA cross-linking was seen following exposure of human fibroblasts to N-acetyoxy-2-acetylaminofluorene and following exposure of mouse embryo cells to 7,12-dimethylbenz[a]-anthracene. No cross-link effect was seen following treatment with N-methyl-N'-nitro-N-nitrosoguanidine, benz-[a]anthracene, benz[A]anthracene-5,6-dihydroepoxide, or metabolic inhibitors. The cross-linking appeared to be DNA-protein in nature since proteinase treatment removed the effect. DNA single-strand breaks were also induced by several of these agents in the case of N-acetoxy-2-acetylaminofluorene and N-methyl-N'-nitro-N-nitrosoguanidine, approximately 70 to 90% of these breaks were rejoined after an 18-hr incubation in fresh medium, whereas repair of the cross-links induced by N-acetoxy-2-acetylaminofluorene was slight at this time.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000494:pharmacology; D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D011506:Proteins / Q000378:metabolism*
D000963:Antimetabolites; D002273:Carcinogens; D004277:DNA, Single-Stranded; D011506:Proteins; D008769:Methylnitronitrosoguanidine; D015127:9,10-Dimethyl-1,2-benzanthracene; D000099:Acetoxyacetylaminofluorene; D004247:DNA