The formation and stability of methyl phosphotriesters in the DNA of rat tissues after treatment with the carcinogen N,N-dimethylnitrosamine.

Following the injection i.p. of N,N-dimethylnitrosamine (DMN) into Chester Beatty (CB) hooded, female rats (2 mg/kg) measurable concentrations of methyl phosphotriesters were found in the DNA of liver, lung and kidney but not in spleen, thymus or brain. In lung and kidney these lesions were stable for at least 14 days but in liver there was a steady loss (t 1/2 9-11 days). Administering the same total dose in 10 weekly injections produced the same concentration of phosphotriesters in lung and kidney DNA as the single injection but in liver only half of the concentration induced by the single injection was found. It was calculated that the half-life of methyl phosphotriesters in the liver DNA of animals given repetitive injections was of the order of 6 weeks.