Effect of combined selenium and retinyl acetate treatment on mammary carcinogenesis

The influence of feeding a pharmacological level of either selenium (SE), retinyl acetate (RA), or selenium and retinyl acetate (SE + RA) on N-methyl-N-nitrosourea-induced mammary carcinogenesis was studied in female Sprague Dawley rats. Rats received 50 mg N-methyl-N-nitrosourea per kg body weight at 50 days of age. Seven days after carcinogen treatment, groups of 25 rats each were placed on laboratory chow diet supplemented with either a placebo or 300 mg RA, 4 mg SE, or 300 mg RA plus 4 mg SE per kg diet. Animals were palpated for detection of mammary tumors twice each week, and the study was terminated 130 days after N-methyl-N-nitrosourea was given. In comparison to the placebo group, treatment with RA or RA + SE reduced tumor incidence, lessened the average number of tumors per rat, and prolonged tumor latency. RA + SE had the greatest inhibitory effect on the carcinogenic process. The effect of combined treatment with RA and SE was additive in nature. The length of the estrous cycle was increased by treatment with RA + SE, and some pathological changes of the ovary and uterus were noted. This investigation provides the first evidence of an additive inhibitory effect resulting from combined treatment with RA and SE.