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Inhibitory Effect of 13-cis-Retinoic Acid on Urinary Bladder Carcinogenesis Induced in C57BL/6 Mice by N-Butyl-N-(4-hydroxybutyl)nitrosamine¹

Life Sciences Division, IIT Research Institute, Chicago, Illinois 60616 [P. J. B., H. J. T., C. J. G., R. C. M.]; Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [R. A. S.]; and Biometry [C. C. B.] and Lung Cancer [M. B. S.] Branch, National Cancer Institute, Bethesda, Maryland 20014

The effect of 13-cis-retinoic acid on the induction of urinary bladder carcinoma by N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) was studied in male C57BL/6 mice. Animals received a total dose of either 90 or 140 mg of OH-BBN via gastric intubations of 7.5 or 10.0 mg of OH-BBN 2 times each week for 6 or 7 weeks, respectively. Seven days after the last OH-BBN intubation, animals were fed laboratory chow diet supplemented with either 200 mg of 13-cis-retinoic acid per kg or its placebo. Animals were killed at 6 months after the first carcinogen intubation. Highly invasive squamous and transitional cell carcinomas of the urothelium were found at autopsy. In the majority of these carcinomas, invasion of the bladder muscle wall by tumor cells had occurred. At the two dose levels of OH-BBN, feeding of 13-cis-retinoic acid reduced the incidence of both carcinomas and noninvasive papillomas, as well as the extent of neoplastic development in the urinary bladder. In mice receiving the lower dose of OH-BBN, the feeding of 13-cis-retinoic acid prevented the appearance of both squamous and transitional cell carcinomas with a reduction in incidence from 33 to 0% (p < 0.01). The results of this study indicate that 13-cis-retinoic acid reduced not only the severity of highly invasive urinary bladder carcinomas but also the incidence of such cancers.

¹ Supported in part by Contract NO1-CP-23292 from the Division of Cancer Cause and Prevention, National Cancer Institute.

² To whom requests for reprints should be addressed, at IIT Research Institute, 10 West 35th Street, Chicago, Ill. 60616.

Received 7/24/78. Accepted 9/13/78.