Evaluation of DNA damage by the alkaline elution technique in liver, kidneys and lungs of rats and hamsters treated with N-nitrosodialkylamines.

Abstract

Induction of single-strand breaks in the DNA of three organs of BD-VI rats and Syrian golden hamsters was examined 4 h after a single i.p. dose of N-nitrosodimethylamine (DMN) or N-nitrosodiethylamine (DEN). Damage was monitored in vivo by the alkaline elution method, in which DNA is dosed fluorometrically. DNA damage was induced by DMN in the liver and kidneys of rats and in the liver and lungs of hamsters, and by DEN in rat and hamster liver. High doses of the hepatocarcinogen and hepatotoxic compound carbon tetrachloride, did not induce DNA damage in rat liver. A correspondence between DNA fragmentation (our study) and tumour induction (reported in the literature) was found in the following organs: rat and hamster liver (DMN, DEN), rat kidney (DMN), rat lung (DMN, DEN), hamster kidney (DMN, DEN). In contrast, no such correlation was observed in rat kidney and hamster lung following DEN-treatment and in hamster lung following DMN-treatment. Thus, the in vivo alkaline elution assay would appear to be most useful for detecting DNA damage by chemicals that are activated metabolically in the liver and that bind to hepatic DNA.