Induction of Uterine Hemangioendothelioma and Lymphoma in (C57BL/6N×C3H/2N)F1 Mice by Oral Administration of Azathioprine

The tumorigenicity of 6-(l-methyl-4-nitro-5-imidazolyl)mercaptopurine (azathioprine), an imniuno-suppressant, was examined in (C57BL/6N×C3H/2N)F1 mice. Animals were divided into 6 groups with 50 mice in each group, and they were given powdered diet mixed with 0, 5 or 20 ppm azathioprine starting at 6 weeks and ending at 100 weeks of age. Female mice, given 20 ppm azathioprine, developed lymphomas and uterine hemangioendotheliomas at incidences of 12.5 and 14.6%, respectively, which were significantly higher than the incidences in control mice (P< 0.05), Lymphoma and uterine hemangioendothelioma developed independently in different mice. On the other hand, the male mice given 20 ppm azathioprine had a significantly (P< 0.05) lower incidence of hepatic tumor (0.5%) compared to the control mice (16%).