Formation of O6-methylguanine in regenerating rat liver by N-nitrosomethylbenzylamine is not sufficient for initiation of preneoplastic foci

The DNA methylating activities of N-nitrosodimethylamine (NDMA), an initiator of hepatic γ-glutamyltranspeptidase-positive foci, and N-nitrosomethylbenzylamine (NMBzA), which does not initiate, were studied in regenerating rat liver. Equimolar doses of 14C-labelled NDMA and NMBzA (33.5 μmol/kg) were administered to male Sprague-Dawley rats 18 h after partial hepatectomy. NDMA and NMBzA both produced 7-methylguanine and O6-methylguanine. The results suggest that although the formation of O6-methylguanine may be necessary it is not sufficient for initiation of preneoplastic foci.