Induction of single-strand breaks and interstrand cross-links in liver DNA after the administration of 2-acetylaminofluorene and trans-4-acetylaminostilbene to rats.
2-Acetylaminofluorene (AAF) or trans-4-acetylaminostilbene (AAS) was orally or intraperitoneally administered to female Wistar rats. DNA from liver cells was analyzed for single-strand breaks by the alkaline elution assay. Only borderline effects were observed with doses (100 mumol/kg) used in animal carcinogenesis experiments. Even high doses of AAF (1,000 mumol/kg) were not effective. Methyl methanesulfonate (MMS) in vivo and gamma irradiation in vitro were shown to produce dose-dependent DNA single-strand breaks (positive control). Only a marginal effect was obtained with 100 mumol/kg MMS. The elution rate of DNA was increased by a factor of 34 in liver cells in vitro with 400 rad of gamma irradiation. Only a fraction of this rate could be demonstrated immediately after irradiation in vivo, and no lesions were found two hours later. This strongly indicates the rapid repair of single-strand breaks. Additional experiments showed that AAS, a nonhepatocarcinogen, produced more interstrand cross-links in the rat liver DNA than did AAF.
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D003432:Cross-Linking Reagents; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013267:Stilbenes / Q000633:toxicity*
D003432:Cross-Linking Reagents; D004277:DNA, Single-Stranded; D013267:Stilbenes; C028520:4-acetylaminostilbene; D015073:2-Acetylaminofluorene