DNA methylation by N-nitrosomethylbenzylamine in target and non-target tissues of NMRI mice.

Abstract

Adult female NMRI mice received a single i.p injection of N-nitroso(methyl-14C)methylbenzylamine (2.5 mg/kg body weight). Multiple weekly applications of such a dose, by this route, have previously been shown to induce lung adenomas and forestomach carcinomas in all experimental animals. After a survival time of 6 h, DNA was isolated from various tissues and analysed for methylated purines by separation of the acid hydrolysate on Sephasorb columns. Highest concentrations of 7-methylguanine and 06-methylguanine were present in hepatic DNA, followed by lung and forestomach. DNA methylation in the oesophagus was only 21% less than in forestomach. Since both tissues develop a high tumour incidence after oral administration of N-nitrosomethylbenzylamine (MBN), this observation suggests that despite their anatomical similarities the level of DNA modification required for malignant transformation differs considerably in these tissue. In the remaining organs, DNA alkylation was either considerably less (colon, glandular stomach, kidney) or not detectable (small intestine, spleen). These date indicate that following i.p. injection in mice, MBN is preferentially metabolised in a non-target organ (liver). Among the various other tissues investigated, highest levels of initial DNA methylation were present in forestomach and lung, i.e., the principal target organs of MBN for this route of application.