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DNA-Protein Cross-Linking by Chemical Carcinogens in Mammalian Cells¹

Department of Physiology, Harvard University School of Public Health, Boston, Massachusetts 02115

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-acetoxy-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.

¹ This investigation was supported by Research Grants CA-11751 and ES-00002 and NIH Training Grant CA-05502.

² Present address: Department of Pathology, Peter Bent Brigham Hospital, Boston, Mass.

³ To whom requests for reprints should be addressed, at Department of Physiology, Harvard University School of Public Health, 665 Huntington Avenue, Boston, Mass. 02115.

Received 4/18/78. Accepted 11/20/78.

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