Summary
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.
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Abbreviations
- 6-MP:
-
6-mercaptopurine
References
Goodman DG, Ward JM, Squire RA, Chu KC, Linhart MS (1979) Neoplastic and nonneoplastic lesions in aging F344 rats. Toxicol Appl Pharmacol 48:237–248
Haseman JK, Huff J, Boorman GA (1984) Use of historical control data in carcinogenicity studies in rodents. Toxicol Pathol 12:126–135
Heddle JA, Hite M, Kirkhart B, Mavournin K, MacGregor JT, Newell GW, Salamone MF (1983) The induction of micronuclei as a measure of genotoxicity. Mutat Res 123:61–118
Heidelberger C, Freeman AE, Pienta RJ, Sivak A, Bertram JS, Casto BC, Dunkel VC, Francis MW, Kakunaga T, Little JB, Schechtman LM (1983) Cell transformation by chemical agents — a review and analysis of the literature. Mutat Res 114:283–385
International Agency for Research on Cancer (1981) Some antineoplastic and immunosuppressive agents. IARC Monogr Eval Carcinog Risk Chem Hum 26:249–266
Kier LD, Brusick DJ, Auletta AE, Von Halle ES, Brown MM, Simmon VF, Dunkel VC, McCann J, Mortelmans K, Prival M, Rao TK, Ray V (1986) TheSalmonella typhimurium/mammalian microsomal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 168:69–240
Koestner A (1986) The brain-tumour issue in long-term toxicity studies in rats. Fd Chem Toxicol 24:139–143
Maekawa A, Kurokawa Y, Takahashi M, Kokubo T, Ogiu T, Onodera H, Tanigawa H, Ohno Y, Furukawa F, Hayashi Y (1983) Spontaneous tumors in F344/DuCrj rats. Gann 74:365–372
Moreland FM, Sheu CW, Springer JA, Green S (1981) Effects of prolonged chemical treatment with cyclophosphamide and 6-mercaptopurine in the dominant lethal test system. Mutat Res 90:193–199
Peto R, Pike MC, Day NE, Gray RG, Lee PN, Parish S, Peto J, Richards S, Wahrendorf J (1980) Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. In: Long-term and short-term screening assays for carcinogens: a critical appraisal [IARC Monogr Suppl 2]. IARC, Lyon, pp 311–426
Preston RJ, Au W, Bender MA, Brewen JG, Carrano AV, Heddle JA, McFee AF, Wolff S, Wassom JS (1981) Mammalian in vivo and in vitro cytogenetic assays. Mutat Res 87:143–188
Solleveld HA, Haseman JK, McConnell EE (1984) Natural history of body weight gain, survival, and neoplasia in the F344 rat. J Natl Cancer Inst 72:929–940
Swenberg JA (1986) Brain tumours — problems and perspectives. Fd Chem Toxicol 24:155–158
Syekora I (1981) Dominant-lethal test of 6-mercaptopurine: dependence on dosage, duration and route of administration. Neoplasma 28:739–746
WHO Scientific Group (1969) Report of the WHO scientific group on principles for the testing and evaluation of drugs for carcinogenicity. WHO Tech Rep Ser 426:1–26
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This study was supported by grants-in-aid for cancer research from the Ministry of Health and Welfare of Japan. Part of this work was presented at the 47th Annual Meeting of the Japanese Cancer Association in Tokyo, September 1988
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Maekawa, A., Nagaoka, T., Onodera, H. et al. Two-year carcinogenicity study of 6-mercaptopurine in F344 rats. J Cancer Res Clin Oncol 116, 245–250 (1990). https://doi.org/10.1007/BF01612898
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DOI: https://doi.org/10.1007/BF01612898