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Cancers of the colon and breast are two of the most prevalent cancers in developed countries. The present experiments were conducted to determine the influence of several dietary doses of grape seed proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis and azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a dual-organ tumor model. In addition, the effects of the grape seed proanthocyanidins on liver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities and on colonic ornithine decarboxylase activity were examined to determine possible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhibition of AOM-induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feeding the grape proanthocyanidins resulted in no significant effect on the activity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. This lack of action on mammary tumorigenesis in part may be due to lack of effect of dietary proanthocyanidins on the liver carcinogen-metabolizing enzymes cytochrome P-450 1A and glutathione S-transferase. These results indicate that grape polyphenolics warrant further evaluation as potential colon cancer chemopreventive agents.

In this study, we report that chronic ethanol intake at 20% of calories can enhance the initiation stage and at 15% of calories can enhance the promotion stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in female Sprague-Dawley rats. Ethanol consumption at 20% of calories by female rats from 25 to 53 days of age was associated with a significant increase in terminal end bud (TEB) structures and a significant decrease in alveolar bud structures of the normal mammary gland. In addition to changes in mammary gland morphology, ethanol consumption at 20% of calories also was associated with a significant increase in incorporation of [3H]thymidine into mammary DNA and a significant increase in the DNA-labeling index of mammary TEB. Therefore, specific ethanol intakes can enhance DMBA-induced mammary tumorigenesis. The enhancement of the initiation stage partly may be explained by alterations in the structural development of the normal rat mammary gland that increase susceptibility to chemically induced mammary tumorigenesis.