RETINOID FEEDING, HORMONE INHIBITION, AND OR IMMUNE STIMULATION AND THE GENESIS OF CARCINOGEN-INDUCED RAT MAMMARY CARCINOMAS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (2) , 585-591
Abstract
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-.beta.-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene) plus 2 bromo-.alpha.-ergocryptine], and/or immune stimulation (methanol-extracted residue of BCG, 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 BCG or cell wall skeleton of N. rubra did not affect mammary carcinoma incidence when administered 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 only. 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 wk after DMBA administration). Although HI was always superior to RA feeding in the prophylaxis of this neoplastic process, a significant synergism between these 2 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 1 exception, immune stimulation did not significantly influence this carcinogenic process, when administered alone or when administered to rats with a reduced mammary carcinoma burden, i.e., animals treated with RA and/or HI.