Effect of retinyl acetate on the incidence of mammary carcinomas and hepatomas in mice

Studies were designed to determine the efficacy of retinyl acetate (RA) in preventing mammary tumorigenesis in C3H-Avy female mice. Mice were fed a stock diet supplemented with RA beadlets at concentrations of 83, 41, and 21 mg/kg diet. Control animals received stock diet supplemented with placebo beadlets. The RA diet was started at conception in 1 group of animals whose mothers were fed RA from the time of mating. Two other groups of animals were placed on the RA diet at weaning or at 3 months of age. Mice were killed and necropsied 1 month after the appearance of the first mammary tumor or at 15 months of age if no tumor developed. No significant difference in incidence of mammary carcinomas was found between control and RA-fed mice. The incidence was 80--90% in all groups. The number of tumors per mouse (1.6--2.1) and the tumor latency period (10.2--11.6 mo) were not influenced by RA in the diet. Two unexpected observations were made: 1) Control mice autopsied at 12 months of age or older showed a 70% incidence of hepatomas, whereas the incidences were approximately 11, 17, and 46% in mice fed 83, 41, and 21 mg RA/kg diet, respectively. 2) Severe damage to most articulations was induced by RA, even at the dose of 21 mg/kg diet, which failed to cause any other sign of toxicity.