The effects of nonspecific stimulation of the reticuloendothelial system by Bacillus Calmette-Guérin (BCG) on rat mammary carcinogenesis were studied. A single feeding of dimethylbenz(a)anthracene (DMBA) to female Sprague-Dawley rats at the age of 50 days induced both an immediate depression of spleen weight and reduction of the number of mononuclear spleen cells and the formation of multiple mammary carcinomas after a latency period of 6 weeks. The spleen weight returned to the control values within 3 weeks of the DMBA feeding, but the number of mononuclear spleen cells remained below the control values throughout the latency period of 6 weeks.

BCG given on the same day as DMBA counteracted the effect of the latter on the spleen. It decreased both amplitude and duration of the carcinogen-induced depression of spleen weight; moreover, it actually increased the absolute number of mononuclear spleen cells above the control values, namely, those recorded in rats receiving neither DMBA nor BCG. When BCG was given before or within 6 weeks (latency period) after the DMBA feeding, spleen weight and spleen cell counts, although usually higher than in animals not receiving BCG, did not exceed the control values. When given 6 weeks after DMBA, BCG slightly increased both parameters above the control values.

Tumor appearance was delayed only in animals treated with BCG on the same day as the DMBA feeding. However, the ultimate tumor incidence in the BCG-treated and untreated groups was similar. When BCG was administered after the appearance of the first tumor, it accelerated the formation of additional tumors. BCG had no effect, in any of these circumstances, on the growth rate of established tumors.

The effect of BCG on the induction of mammary tumors by DMBA did not seem to be mediated through endocrine mechanisms.

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Supported in part by the Fonds Cancérologique de la Caisse Générale d'Epargne et de Retraite and in part by the Contract of the Ministère de la Politique Scientifique within the framework of the Association Euratom, University of Brussels, and University of Pisa.

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