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Retinoid Feeding, Hormone Inhibition, and/or Immune Stimulation and the Genesis of Carcinogen-induced Rat Mammary Carcinomas¹

Department of Anatomy, Michigan State University, East Lansing, Michigan 48824

Female Sprague-Dawley rats were treated at 53 days of age with a single intubation of 7,12-dimethylbenzanthracene (DMBA). Three days after carcinogen treatment, the animals were treated with retinyl acetate (RA) (at 3 dietary levels), hormone inhibition (HI) [tamoxifen (1-p-β-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene) plus 2 bromo--ergocryptine], and/or immune stimulation (methanol-extracted residue of iBacillus Calmette-Guérin, cell wall skeleton of Nocardia rubra, or cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant). RA at 0.6 or 1.0 mM concentrations per kg diet significantly reduced the incidence of mammary carcinomas; 0.2 mM concentrations of RA per kg diet did not affect tumor incidence. HI also significantly decreased mammary carcinoma incidence, an effect which was significantly enhanced by all 3 dietary levels of RA. Immune stimulation by methanol-extracted residue of Bacillus Calmette-Guérin or cell wall skeleton of Nocardia rubra did not affect mammary carcinoma incidence when administered either alone or in combination with RA and/or HI. The cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant significantly reduced mammary carcinoma incidence in rats fed RA but did not affect mammary carcinoma incidence in placebo-fed rats or in rats treated only with HI. However, in rats treated with the triple combination of cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant, RA, and HI, no mammary carcinomas were observed for the duration of treatment (20 weeks after DMBA administration). Although HI was always superior to RA feeding in the prophylaxis of this neoplastic process, a significant synergism between these two treatments was consistently observed. This distinct synergism was observed even when using the low dietary level of RA, an amount of RA which by itself was ineffective in the suppression of mammary carcinogenesis. With but one exception, immune stimulation did not significantly influence this carcinogenic process, either when administered alone or when administered to rats with a reduced mammary carcinoma burden, i.e., animals treated with RA and/or HI.

¹ Supported by USPHS Contract N01-CP-05717 from the Division of Cancer Cause and Prevention, National Cancer Institute.

Received 6/ 1/82. Accepted 10/11/82.

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