DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion.
Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of [14C]N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.
D000225:Adenine / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000494:pharmacology*; D006147:Guanine / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D006147:Guanine; D004247:DNA; D000225:Adenine; D004128:Dimethylnitrosamine