INHIBITION OF URINARY-BLADDER CANCER BY N-(ETHYL)-ALL-TRANS-RETINAMIDE AND N-(2-HYDROXYETHYL)-ALL-TRANS-RETINAMIDE IN RATS AND MICE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (3) , 933-936
Abstract
The chemopreventive activity of 2 synthetic retinamides of relatively low toxicity against N-butyl-N-(4-hydroxybutyl)nitrosamine(OH-BBN)-induced urinary bladder cancer was studied in F344 rats and C57BL/6 .times. DBA/2 F1 mice. Female and male rats were given a total dose of 1800 or 3200 mg OH-BBN over a period of 6 or 8 wk, respectively. Male mice were given a total dose of 90 or 180 mg OH-BBN over 9 wk. Seven days after the final intubation of OH-BBN, animals were fed a placebo diet or a diet supplemented with the following retinoids: for rats, 0.8 mmol 13-cis-retinoic acid, 2 mmol N-(ethyl)-all-trans-retinamide or 2 mmol N-(2-hydroxyethyl)-all-trans-retinamide per kg diet; and for mice, 0.5 or 1.0 mmol of N-(ethyl)-all-trans-retinamide or N-(2-hydroxyethyl)-all-trans-retinamide per kg diet. Animals were killed 6 mo. after the initial gastric intubation. In comparison to male and female rats fed placebo diets, all 3 retinoids reduced the incidence, number and severity of the low-grade papillary transitional cell carcinomas of the urinary bladder. Treatment of mice with either of the 2 retinamides reduced the incidence of highly invasive urinary bladder carcinomas. The chemopreventive effect of the less toxic retinamides was equal to or greater than that of 13-cis-retinoic acid.