Induction of uterine hemangioendothelioma and lymphoma in (C57BL/6N x C3H/2N)F1 mice by oral administration of azathioprine

The tumorigenicity of 6-(1-methyl-4-nitro-5-imidazolyl)mercaptopurine (azathioprine), an immunosuppressant, was examined in (C57BL/6N X 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 less than 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 less than 0.05) lower incidence of hepatic tumor (0.5%) compared to the control mice (16%).