Effect of long-term administration of retinoids on rats exposed transplacentally to ethylnitrosourea

A neurogenic cancer model, involving transplacental administration of ethylnitrosourea (ENU) to Sprague-Dawley rats, was employed to evaluate the efficacy of retinyl acetate, 13-cis-retinoic acid, and all-trans-retinoic acid in prevention of nervous system tumors in the offspring. Supplementation of the diet with either of these retinoids did not alter the incidence, number, or latency period of the induced neurogenic tumors. Long-term administration of high doses of 13-cis-retinoic acid (240 mg/kg of diet) or all-trans-retinoic acid (65 mg/kg of diet) produced lethal toxicity in this strain of rats, possibly due to interference with vitamin K absorption and the resulting internal hemorrhages associated with hypoprothrombinemia. Prolonged feeding of retinyl acetate increased the retinyl palmitate level in the liver. The concentration reached was not dose-dependent; a maximum level (approximately 10-fold that of controls) was observed after six months of feeding. An unexpected observation was the decrease in liver retinyl palmitate concentration in the livers of rats fed 13-cis-or all-transretinoic acid.