N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE-INDUCED URINARY-BLADDER CANCER IN C57BL-6 X DBA-2F1 MICE AS A USEFUL MODEL FOR STUDY OF CHEMOPREVENTION OF CANCER WITH RETINOIDS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (3) , 927-932
Abstract
Highly invasive carcinomas of the urinary bladder were induced in male C57BL/6 .times. DBA/2 F1 (B6D2F1) mice by gastric intubation of N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN) using a quantitative dosing schedule. Animals received 5 or 10 mg OH-BBN/intubation, 2 times each week, for 9 wk for a total dose of 90 or 180 mg; they were killed 6 mo. after the first carcinogen intubation. Seven days after the final intubation of OH-BBN, animals were fed a placebo diet or diet supplement with 150 or 200 mg 13-cis-retinoic acid/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. A total of 67% of the carcinomas induced in these animals invaded 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 and other compounds.