Chemoprevention of 2-amino-1-methyl-6-phenyli-midazo 4,5-b pyridine-induced carcinogen-DNA adducts by Chinese cabbage in rats.

Abstract

AIM:The food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo 4,5-b pyridine (PhIP) induces colon and mammary gland tumors in rats and has been implicated in the etiology of human colorectal cancer.This study was conducted to examine the potentially preventive effect of Chinese cabbage (Brassica chinensis),a brassica vegetable most commonly consumed in China, against this carcinogen-induced DNA adduct formation in rats and its possible mechanisms.METHODS:Sprague-Dawley rats were maintained for 10 days on basal diet or diet containing 20% (w/w) freeze-dried cabbage powder prior to administration of a single dose of PhIP (10mg/kg) by oral gavage. Rats were sacrificed at 20h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung and liver were analyzed using (32)P-postlabeling technique. Levels of hepatic cytochrome P450 (CYP)1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7-methoxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases (GSTs) towards 1-chloro-2, 4-dinitrobenzene (CDNB) in the liver, lung and colon were measured.RESULTS:Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced levels of PhIP-DNA adducts in the colon, heart, lung and liver, with inhibition rates of 82.3%, 60.6%, 48.4% and 48.9%, respectively (P< 0.01). The enzyme assays revealed that Chinese cabbage induced both CYP1A1 and 1A2 activity, but the induction was preferential for CYP1A1 over 1A2 (81% vs 51%).GST activity towards CDNB in the liver and lung, but not colon, was also significantly increased by cabbage treatment.CONCLUSION:The results indicate that Chinese cabbage has a preventive effect on PhIP-initiated carcinogenesis in rats and the mechanism is likely to involve the induction of detoxification enzymes.