Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite

Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one-half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination.