CHEMOPROTECTION AGAINST THE FORMATION OF COLON DNA-ADDUCTS FROM THE FOOD-BORNE CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN THE RAT

The mutagenic heterocyclic aromatic amine, 2-amina-1-methyl-6-phenylim idazo[4,5-b]pyridine (PhIP), is a pyrolysis product in cooked foods th at has been shown to be a rat colon carcinogen and has been implicated in the etiology of human colon cancer. In order to identify chemoprot ection strategies that could be carried out in humans, a pilot study w as conducted in which PhIP-DNA-adduct levels were quantified in the co lons of male F344 rats that had been subjected to 16 different putativ e chemoprotection regimens, followed by a gavage of PhIP (50 mg/kg) an d sacrifice 24 h later. The 16 treatments (Oltipraz, benzylisothiocyan ate, diallyl sulfide, garlic powder, ethoxyquin, butylated hydroxyanis ole, glutathione, indole-3-carbinol, alpha-angelicalactone, kahweol/ca festol palmitates, quercetin, green tea, black tea, tannic acid, amyla se-resistant starch, and physical exercise) comprised sulfur-containin g compounds, antioxidants, flavonoids, diterpenes, polyphenols, high d ietary fiber, etc. The strongest inhibition of PhIP-DNA adduct formati on in the colon was observed upon pretreatment with black. tea, benzyl isothiocyanate, and a mixture (1:1) of kahweol:cafestol palmitates, wh ich resulted in 67, 66, and 54% decreases in colon PhIP-DNA adduct lev els, as compared with controls. Preliminary studies on their mechanism of action indicated that only kahweol:cafestol caused a substantial i nduction of glutathione S-transferase isozymes (GSTs) that are thought to be important in the detoxification of PhIP. Notably, this inductio n occurred in the liver rather than in the colon.