Tissue-specific inhibition of [3H]thymidine incorporation into DNA by carcinogenic N-nitrosamines.
The N-nitrosamines N-nitrosodimethylamine (DMN), N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were injected intraperitoneally 24 h before sacrifice in F344 rats and C57BL mice in doses of 297 mumoles/kg b.w. and 148 mumoles/kg b.w., respectively. 2 h before sacrifice, the animals were given an intraperitoneal injection of [3H]thymidine. The results showed that the examined N-nitrosamines inhibited the incorporation of [3H]thymidine into DNA in a few tissues of the rats and the mice. The results indicated that the N-nitrosamines exerted a tissue-specific inhibition of the [3H]thymidine incorporation in the tissues reported to be involved in the biotransformation of these substances. The observed inhibitory effects on the incorporation of [3H]thymidine by DMN, NNN and NNK were also correlated to a considerable extent to the reported sites of carcinogenicity. The present study indicates that measurements of [3H]thymidine incorporation into DNA in various tissues of experimental animals is a useful short-term bioassay to evaluate the potential tissue-specific carcinogenicity of the N-nitrosamines. The method may also be useful as a complement to other short-term in vivo tests in the screening of potential genotoxicity of several other chemicals.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013936:Thymidine; D014018:Tissue Distribution
D002273:Carcinogens; D009602:Nitrosamines; D004247:DNA; D013936:Thymidine