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Inhibition of Growth of Established N-Methyl-N-nitrosourea-induced Mammary Cancer in Rats by Retinoic Acid and Ovariectomy¹

Clinical Research Institute of Montreal and Department of Medicine, University of Montreal, Montréal, Québec, H2W 1R7, Canada

Retinoids are effective in the prevention of N-methyl-N-nitrosoureainduced mammary carcinoma; retinoids and hormonal therapy exert synergy in cancer prevention. In this study, we examined the effects of the dietary supplementation with all-trans retinoic acid (RA) alone or in combination with ovariectomy on the growth of established N-methyl-N-nitrosourea-induced mammary carcinomas in rats. In the first experiment, animals (n = 13) were entered in each of the following treatment groups when their tumors reached 2 cm in diameter: 1, control diet; 2, RA 300 mg/kg diet; 3, ovariectomy (OVX); 4, RA 300 mg/kg diet plus OVX. Animals were sacrificed after 28 days of therapy. In the RA-supplemented animals, tumor progression was less than in the control group without signs of toxicity as assessed by total and individual tumor surface area and weight, and animal weight. OVX produced tumor regression that was not enhanced by the addition of RA. In a second experiment, RA 65- and 130-mg/kg diets were dissolved in corn oil with antioxidants prior to mixing to the diet to improve biodisponibility. This resulted in overall stabilization of tumor growth by RA addition to the diet at either of the 2 doses utilized; the addition of RA 65 mg/kg diet did not modify tumor regression induced by OVX. In conclusion, the dietary supplementation with RA decreased the progression or stabilized the growth of the majority of tumors and only rarely (6 %) induced tumor regression; no additive or synergistic effects were found with the combination of RA and ovariectomy.

¹ This work was supported by a grant from the National Cancer Institute of Canada.

² To whom requests for reprints should be addressed, at Clinical Research Institute of Montreal, 110 Pine Avenue West, Montréal, Québec, H2W 1R7, Canada.

Received 11/22/89. Accepted 6/19/90.

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