Azathioprine induction of lymphomas and squamous cell carcinomas in rats

The carcinogenicity of azathioprine was evaluated in weaning female noninbred Sprague-Dawley rats by feeding it in the diet. Due to toxicity, the dose had to be changed during the course of the experiments and ranged from 0.015 to 0.04% of the diet by weight. In the first experiment, the estimated maximal cumulative consumption of azathioprine was 1.5 g/rat. Of the 14 rats evaluated, six developed thymic lymphomas, and four developed squamous cell carcinomas of the ear duct. When the experiment was repeated with a slightly lower daily consumption but with a cumulative total dose of 2.2 g/rat, there were seven of 19 rats with thymic lymphoma and two rats with ear duct carcinoma. These data support the hypothesis that azathioprine is a carcinogen.