Two-year carcinogenicity study of 6-mercaptopurine in F344 rats

The carcinogenicity of 6-mercaptopurine (6-MP), an anticancer drug, was examined in F344 rats of both sexes, administered the chemical at dietary levels of 0 (control), 25 ppm or 50 ppm for 2 years. Many tumors developed in all groups including the control group, the organ distribution and histological types being similar to those reported for spontaneous lesions. In males, there was no significant increase in the incidence of any tumor in the treated groups over that in the control group. In females, however, positive trends were noted in the occurrence of C-cell tumors, pheochromocytomas, uterine adenocarcinomas and gliomas, and the incidences of C-cell tumors and pheochromocytomas in the 50 ppm group were significantly higher than the values in the respective control group. In addition, the total numbers of malignant tumors increased significantly in the female 50 ppm group. However, most of the tumors demonstrating increase are frequently observed spontaneous lesions in this strain of rats, and their incidences in the present female control group were lower than in our historical data. In addition, there were no significant differences in the incidences of preneoplastic changes and induction times for the above-listed tumors between the female control and the 50 ppm groups. These results thus indicated that while the carcinogenic potential of 6-MP can not be precluded, it can be only very weak or marginal, after continuous administration in the diet at the 50 ppm level for 2 years. The leukemogenic action of 6-MP was negative under the present experimental conditions.