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.