Carcinogenesis by derivatives of 1-nitroso-3,5-dimethylpiperazine in rats.

Four mononitrosopiperazines were administered to groups of 20 female Fischer 344 rats to compare their effectiveness as carcinogens. The four, 1-nitroso-3,5-dimethylpiperazine, its 4-acetyl derivative, its 4-benzoyl derivative, and 1-nitroso-3,4,5-trimethylpiperazine, were given as 0.7 mM solutions in drinking water, 100 ml to each rat per week. The length of treatment varied from 26 weeks for nitrosotrimethylpiperazine to 50 weeks for 1-nitroso-3,5-dimethyl-4-benzoylpiperazine. Dimethyl- and trimethylnitrosopiperazine gave rise to virtually 100% incidence of undifferentiated lymphomas of the thymus and leukemias within 30 weeks (in contrast to the non-C-methylated analogs which are noncarcinogenic or only weakly so). Acetyldimethylnitrosopiperazine was also a potent carcinogen, all of the rats treated with it dying within 30 weeks with tumors of the esophagus. In contrast, benzoyldimethylnitrosopiperazine was weakly carcinogenic, inducing only a small number of tumors of the forestomach and reducing the normal life span of the rats very little.