Effect of grape seed proanthocyanidins on colon aberrant crypts and breasttumors in a rat dual-organ tumor model

Cancers of the colon and breast are two of the most prevalent cancers in de veloped 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 (A OM)-induced colonic aberrant crypt foci (ACF) formation in a dual-organ tum or model. In addition, the effects of the grape seed proanthocyanidins on l iver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities a nd on colonic ornithine decarboxylase activity were examined to determine p ossible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhi bition of AOM-induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feed ing the grape proanthocyanidins resulted in no significant effect on the ac tivity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat ma mmary tumorigenesis. This lack of action on mammary tumorigenesis in part m ay be due to lack of effect of dietary proanthocyanidins on the liver carci nogen-metabolizing enzymes cytochrome P-450 IA and glutathione S-transferas e. These results indicate that grape polyphenolics warrant further evaluati on as potential colon cancer chemopreventive agents.