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Effect of Moderate Vitamin A Supplementation and Lack of Dietary Vitamin A on the Development of Mammary Tumors in Female Rats Treated with Low Carcinogenic Dose Levels of 7,12-Dimethylbenz(a)anthracene¹

Departments of Food Science and Human Nutrition [M. H. Z., M. E. C., I. A. R.] and Anatomy [J. V. D., C. W. W.], Michigan State University, East Lansing, Michigan 48824

We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12-dimethylbenz(a)anthracene. The number of mammary tumors was significantly (P < 0.05) reduced if prior to and during initiation with 7,12-dimethylbenz(a)anthracene the rats were fed a moderately increased (30 µg/day) or marginal (3 µg/day) amount of vitamin A, compared to rats fed an adequate (10 µg/day) amount of vitamin A. The number of mammary tumors was also significantly (P < 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly (P < 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum-fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant (P < 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 µg/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 µg/day) intake of vitamin A, that resulted in a small, but statistically significant (P < 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors.

These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development.

¹ Supported by a grant from the NIH (ROI CA33190) and in part by grants from the United States Department of Agriculture (81-CRCR-1-0700 and 84-CRCR-1-1377). This publication is Michigan Agricultural Experiment Station Article No. 11879.

² To whom requests for reprints should be addressed.

Received 12/ 4/85. Revised 3/18/86. Accepted 4/ 7/86.

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