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N-Butyl-N-(4-Hydroxybutyl)nitrosamine-induced Urinary Bladder Cancer in C57BL/6 x DBA/2 F₁ Mice as a Useful Model for Study of Chemoprevention of Cancer with Retinoids¹

IIT Research Institute, Chicago, Illinois 60616 [P. J. B., H. J. T., R. C. M.]; University of Maryland School of Medicine, Baltimore, Maryland 21201 [J. M. S.]; and National Cancer Institute, Bethesda, Maryland 20205 [C. C. B., M. B. S.]

Highly invasive carcinomas of the urinary bladder were induced in male C57BL/6 x DBA/2 F₁ (hereafter called B6D2F₁) mice by gastric intubation of N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN) using a quantitative dosing schedule. Animals received either 5 or 10 mg OH-BBN per intubation, two times each week, for 9 weeks for a total dose of either 90 or 180 mg, and they were killed 6 months after the first carcinogen intubation. Seven days after the final intubation of OH-BBN, animals were fed either a placebo diet or diet supplemented with either 150 or 200 mg 13-cis-retinoic acid per kg of diet. A 41 and 43% incidence of urinary bladder cancer was observed in mice given the low and high dose of carcinogen, respectively, and fed a placebo diet. Sixty-seven % of the carcinomas induced in these animals invaded either into or through the urinary bladder wall. Varying degrees of transitional and either squamous or glandular or both squamous and glandular differentiation were observed in the carcinomas. Feeding of diet supplemented with 13-cis-retinoic acid reduced cancer incidence; the degree of reduction was proportional to the dose of retinoid administered. The highly invasive nature of the carcinomas induced by quantitative administration of OH-BBN in B6D2F₁ mice provides a useful animal model of the highly invasive variant of human transitional cell urinary bladder cancer in which to study chemoprevention by retinoids as well as other compounds.

¹ Supported in part by Contract N01-CP-23292 from the Division of Cancer Cause and Prevention, National Cancer Institute.

² Present address: Food and Drug Research Laboratories, Inc., P. O. Box 107, Route 17C, Waverly, N. Y. 14892. To whom requests for reprints should be addressed.

³ Present address: University of New Hampshire, Durham, N. H. 03842.

Received 1/25/80. Accepted 12/ 4/80.

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