Persistence of alkylated DNA bases in the Mongolian gerbil (<i>Meriones unguiculatus</i>) following a single dose of methylnitrosourea

Abstract

Methylated purines were determined in DNA of various gerbil tissues following a single i.v. injection of N-[14C]methyl-N-nitrosourea (10 mg/kg). Enzymic removal of the promutagenic base O6-methylguanine was most efficient in the liver, followed by kidney, lung and brain. In cerebral DNA, 40% of the initial concentration was still present after 6 months. Since the gerbil brain is apparently not susceptible to the oncogenic effect of methylnitrosourea and related carcinogens, these data indicate that the formation and persistence of O6-alkylguanine may constitute a necessary although not sufficient event for the initiation of organ-specific carcinogenesis by monofunctional alkylating agents.