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 gamma-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 mumol/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.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D006147:Guanine; C008450:7-methylguanine; C014707:nitrosobenzylmethylamine; C008449:O-(6)-methylguanine; D004128:Dimethylnitrosamine