DNA alkylation by nitrosobis-(2-oxopropyl)amine in rats of different ages.

We have examined the methylation of liver DNA (O6- and N7-methylguanine) by nitrosobis-(2-oxopropyl)amine (BOP) in male and female rats at various ages, following treatment with 2.5 mg of BOP; this dose given twice weekly for 30 weeks induces tumors in all animals. Except in young rats there was more methylation in female rat liver than in male rat liver, when adjusted for different sizes of the animals. There were differences in the extent of methylation between young (4 weeks) and older rats, but not between young adult (20 weeks) and old adult (65 weeks) males; the latter developed liver tumors when treated with BOP, and the former did not. There was no obvious relation between increased susceptibility to liver tumor induction by BOP and the extent of alkylation of liver DNA. Methylation of DNA was lower in the kidney than in the liver and, here, there was little difference between the sexes. In the testis there was N7-methylation of guanine in DNA, but no O6-methylguanine was detected.