Dose- and Cell Cycle-Dependent O super(6)-Methylguanine Elimination From DNA in Regenerating Rat Liver After ( super(14)C)Dimethylnitrosamine Injection

To study relations between increased transformation sensitivity during DNA synthesis and carcinogen-induced molecular DNA alterations in regenerating liver, the kinetics of formation and the persistence of alkylated DNA bases were determined 10 to 240 min after a single ( super(14)C)dimethylnitrosamine (DMN) injection (1.43 and 4.0 mg/kg) during G sub(1) and in synchronized S phase. The faster elimination of the promutagenic O super(6)-methylguanine during DNA synthesis could represent an important but, because of its saturation at higher carcinogen dosages, not sufficiently effective mechanism to protect proliferating cells from initiation during the most critical period of the cell cycle.