2-YEAR CARCINOGENICITY STUDY OF 6-MERCAPTOPURINE IN F344 RATS
2-YEAR CARCINOGENICITY STUDY OF 6-MERCAPTOPURINE IN F344 RATS
复制标题
DOI：
10.1007/bf01612898
复制
发表时间：
1990-01-01
影响因子：
3.6
通讯作者：
HAYASHI, Y
中科院分区：
文献类型：
--
作者：
MAEKAWA, A;NAGAOKA, T;HAYASHI, Y
一种抗癌药物6-巯基嘌呤（6-MP）的致癌性在F344只雌雄老鼠身上进行了研究，这些老鼠在2年的时间里以0（对照）、25 ppm或50 ppm的饮食水平服用这种化学物质。在包括对照组在内的所有组中都发生了许多肿瘤，器官分布和组织学类型与报道的自发病变相似。在男性中，与对照组相比，治疗组的任何肿瘤发病率都没有显著增加。然而，在女性中，c细胞瘤、嗜铬细胞瘤、子宫腺癌和胶质瘤的发生率呈阳性趋势，50 ppm组的c细胞瘤和嗜铬细胞瘤的发生率显著高于相应的对照组。此外，女性50 ppm组的恶性肿瘤总数显著增加。然而，在该品系的大鼠中，大多数肿瘤的增加是经常观察到的自发病变，并且它们在当前雌性对照组中的发病率低于我们的历史数据。此外，在女性对照组和50 ppm组之间，上述肿瘤的瘤前变化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50 ppm水平的饮食中连续服用2年后，其致癌潜力可能非常微弱或微乎其微。在本实验条件下，6-MP的致白血病作用为阴性。
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.