N-Propyl-N-nitrosourea is a strong leukemogen that induces myelogenic
leukemia in Donryu rats and thymic
lymphoma in F344 rats when administered in
drinking water. In the present study, a single or multiple doses of PNU (total 500 mg/kg
body weight) was given to young male and female F344 rats via a stomach tube. The results demonstrated that the percentage of
tumor-bearing rats was 100% in all PNU-treated male groups, while that of the control group was 46%. Predominant
tumors induced by PNU in male rats were lung
adenoma/
adenocarcinoma followed by peritoneal
mesothelioma, and forestomach
papilloma. In females, the
tumor incidence of PNU-treated groups varied between 58% and 92% while that of the control group was 42%. Although
pituitary tumor was the most frequent
tumor in PNU-treated female rats, it was thought to be spontaneous since its incidence in each experimental group was not statistically different from that of the control group. Lung
tumors and forestomach
papillomas were also induced by PNU in female rats. No thymic
lymphoma, however, was found in any of the PNU-treated groups of either sex. Lung
tumors developed in almost all PNU-treated male rats and in about one-third of PNU-treated female rats.
Mesothelioma was induced only in male rats, and its incidence depended on the treatment schedule. Induced
mesotheliomas were extensively examined histologically, histochemically, immunohistochemically, and electron microscopically.