DNA Alkylation and Tumor Induction in Regenerating Rat Liver After Cell Cycle-Related Continuous N-Nitrosodimethylamine Infusion 1,2,3

ABSTRACT-Synchronized regenerating rat liver after partial hepatec-tomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of [14CjN-nitrosodimethyl-amine (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 G, phase, hydroxyurea-synchronized DNA synthesis, or the G2 +M-phase of re-generating liver or to untreated rats (Go-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 Go-phase liver, with a decrease in the G, phase, the S-phase, and the G2 +M-phase. After continuous DMN exposure, the 06-methylguanine:7-methylguanine ratio was lower in the S-phase and G2 +M-phase livers than in the Go-phase and G,-phase livers, indicating an increased 06-methylguanine repair during DNA synthesis and the G2 +M-phase. Liver tumors in rats treated by continuous DMN infusion either during the Go phase or the S-phas