Effects of age and ethanol on DNA single-strand breaks and toxicity induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or n-nitrosodimethylamine in hamster and rat liver

Abstract

The effects of age and ethanol exposure on liver DNA single-strand breaks (SSB) and liver cell injury induced in hamsters and rats by a single equimolar dose (0.39 mmol/kg) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosodimethylamine (NDMA) were investigated. NNK induced more DNA SSB (by 10–50%) than NDMA in the liver of adult hamsters and rats, but similar differences were not observed in newborn animals. Nitrosamine-induced hepatic DNA damages was compared in newborn and adult animals. While newborn hamsters were less sensitive to NNK-induced DNA damage than adult hamsters, newborn rats were more sensitive to NDMA-induced DNA damage than adult rats. In utero ethanol exposure did not alter significantly the induction of hepatic DNA SSB by NNK or NDMA compared to newborn hamsters and rats. Interestingly, species differences in the extents of NNK-induced hepatic DNA SSB and toxicity were observed in ethanol-consuming adult hamsters and rats. Ethanol treatment of hamsters caused a significant reduction (by 35%) of the frequency of hepatic DNA SSB and a 3.5-fold enhancement of hepatotoxicity induced by NNK.