Effect of pretreatment of rats with N-methyl-N-nitrosourea on the repair of O(6)-methylguanine in liver DNA.

Abstract

The capacity of rat liver to repair O6-methylguanine was determined by measuring the amounts of this base present in DNA after administration of N-[14C]methyl-N-nitrosourea (MNU). Chronic pretreatment of animals with unlabelled MNU either once weekly for 5 weeks or daily on weekdays for 14 days had either no marked effect or inhibited (or overloaded) repair activity, respectively. Pretreatment of rats with single doses of MNU initially decreased O6-methylguanine repair but this effect was lost as the pretreatment interval increased and by 40 h, activity had returned to control values. Administration of methylmethanesulphonate for 14 days had no effect on the removal of O6-methylguanine produced in liver DNA by [14C]MNU. None of the pretreatment schedules inhibited the removal of 3-methyladenine from liver DNA. These effects are contrasted with those produced by pretreatment of rats with dimethylnitrosamine (DMN) or 1,2-dimethylhydrazine which enhanced the capacity of the liver to remove O6-methylguanine produced by single dose of [14C]DMN.