Maekawa A, Nagaoka T, Onodera H, Matsushima Y, Todate A, Shibutani M, Ogasawara H, Kodama Y, Hayashi Y
Division of Pathology, National Institute of Hygienic Sciences, Tokyo, Japan.
J Cancer Res Clin Oncol. 1990;116(3):245-50. doi: 10.1007/BF01612898.
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.
对一种抗癌药物6-巯基嘌呤（6-MP）的致癌性进行了研究，以0（对照）、25 ppm或50 ppm的饮食水平对F344大鼠雌雄两性给药2年。所有组包括对照组都出现了许多肿瘤，其器官分布和组织学类型与报道的自发病变相似。在雄性中，治疗组中任何肿瘤的发生率与对照组相比均无显著增加。然而，在雌性中，观察到C细胞瘤、嗜铬细胞瘤、子宫腺癌和神经胶质瘤的发生呈阳性趋势，50 ppm组中C细胞瘤和嗜铬细胞瘤的发生率显著高于各自对照组的值。此外，雌性50 ppm组中恶性肿瘤的总数显著增加。然而，显示增加的大多数肿瘤是该品系大鼠中常见的自发病变，并且它们在当前雌性对照组中的发生率低于我们的历史数据。此外，雌性对照组和50 ppm组之间上述肿瘤的癌前病变发生率和诱导时间没有显著差异。因此，这些结果表明，虽然不能排除6-MP的致癌潜力，但在以50 ppm的水平在饮食中连续给药2年后，其致癌潜力可能非常微弱或处于边缘水平。在目前的实验条件下，6-MP的致白血病作用为阴性。
