Selective accumulation of O6-methylguanine in DNA of rat bladder epithelium after intravesical administration of N-methyl- N-nitrosourea

Abstract

Summary The amounts of 7-methylguanine, O 6 -methylguanine and 3-methyladenine in DNA of rat bladder epithelium after intravesical administration of N -methyl- N -nitrosourea (MNU) have been determined. After a single dose of 0.5 mg of MNU, O 6 -methylguanine was removed from DNA at slower rates than 3-methyladenine and 7-methylguanine. Furthermore, O 6 -methylguanine was found in increasing amounts in DNA after 4 weekly doses of 0.5 mg of MNU. In other studies, we have shown that 0.5 mg of MNU given once a week for 4 weeks yields a high incidence of transitional cell carcinoma of the bladder in rats. These data suggest that the persistence of O 6 -methylguanine in DNA might be involved in the induction of bladder cancer by MNU.