N-Acetyltransferase multiplicity and the bioactivation of N-arylhydroxamic acids by hamster hepatic and intestinal enzymes

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Abstract
Two groups of female ACI rats were placed on powdered AIN-76 diets containing retinyl acetate (412000 i.u. per kg diet) and two groups of rats were placed on placebo diets. Two weeks later one group from each diet was subcutaneously implanted with a 20 mg pellet containing 1 mg of 17α-ethinylestradiol (EE2) mixed with cholesterol, and the remaining groups received 20 mg cholesterol pellet implants. The four groups of animals were maintained on their respective diet for 24 weeks after pellet implantation. The EE2-treated rats were hyperphagic and weighed less than the cholesterol-treated rats. Retinyl acetate had no effect on food consumption or body wt changes. None of the rats that received pellets composed of cholesterol only exhibited mammary carcinomas (MC) or pituitary tumors. All rats with an EE2 implant had pituitary tumors: 88% of the rats on the placebo diet had one or more MC; 70% of the rats on the retinyl acetate diet had one or more MC. The difference between the two EE2-treated groups for incidence of animals with at least one MC was not significant (x2). However, the EE2-treated rats on the placebo diet had approximately twice as many MC as the EE2-treated rats on the retinyl acetate diet. Thus, retinyl acetate inhibited estrogen-induced mammary carcinogenesis in female ACI rats, without evidence of gross toxicity.