Inhibitory effect of an oxygenated cholesterol on the induction and progression of DMBA-induced mammary carcinomas in the rat

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Abstract
In vivo studies on the effect of two stereoisomeric 7,22-dihydroxycholesterols on tumor development were conducted in the Charles Huggins animal cancer model (DMBA-induced mammary cancer in the Sprague-Dawley female rat). Three groups of DMBA-treated animals were fed a 9:1 mixture of (22R)-cholest-5-ene-3β,7β,22-triol and (22R)- cholest-5-ene-3β,7α,22-triol in the drinking water in a calculated dose of 250 μg per animal per day. One group (A) received the sterols throughout the experimental period of 35 weeks, another group (B) during the first 12 weeks only, and a third group (C) only during weeks 13 through 35 after DMBA injection. Tumor rates and tumor yields were calculated, and statistical assessment by accepted methods demonstrated a very significant inhibitory effect on tumor development in Groups A and B, as compared with Group C. The results indicate a growth-inhibitory effect during the induction period of carcinoma development. The influence on neoplastic growth of (22R)-cholest-5-ene-3β,7α,22-triol, (22R)-cholest-5-ene-3β,7β,22-triol, and (22R)-cholest-5-ene-3β,22-diol-7-one was examined in suspension cultures of Ehrlich ascites tumor cells. The 7α-hydroxy compound proved to be ineffective, whereas the latter two substances displayed a strong cytotoxic effect.