[Chemoprotection by green tea against the formation of food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP)-DNA adducts in rats].
OBJECTIVE
The food-borne mutagen 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 cancer, particularly colorectal cancer. This study was conducted to examine the potential chemopreventive effect of Chinese green tea against PhIP-DNA adduct formation in rats and its possible mechanisms.


METHODS
Sprague-Dawley rats were maintained on freshly prepared aqueous extract of Chinese green tea (3%) or tap water as the sole source of drinking fluid for 10 days prior to administration with a single dose of PhIP (10 mg/kg body wt) by oral gavage. Rats were sacrificed at 20 h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung, and liver were analyzed using 32P-postlabeling technique. The activity of cytosolic glutathione S-transferases (GSTs) in the liver, lung and colon mucosa was also determined using CDNB as substrate.


RESULTS
The levels of PhIP-DNA adducts in the four tissues of rats treated with PhIP alone were highest in the colon (53 +/- 9 adducts/10(8) nucleotides), followed by heart (41 +/- 14 adducts/10(8) nucleotides) and lung (22 +/- 5 adducts/10(8) nucleotides), but much lower in the liver (5 +/- 3 adducts/10(8) nucleotides). Rats pre-treated with green tea had significantly reduced levels of PhIP-DNA adducts, with the inhibition rates being 59%-80%, respectively. While the organ distribution profile of the adducts was not altered by tea treatment as compared with controls given PhIP alone. The GST activity towards CDNB in hepatic, colonic and lung cytosols appear not to be modified by drinking green tea.


CONCLUSIONS
These results support a protective role for green tea against PhIP-initiated carcinogenesis in rats and suggest that consumption of green tea may have significant impact in chemoprevontion against human cancer presumably related to PhIP and other heterocyclie amines.
D000818:Animals; D002273:Carcinogens; D018736:DNA Adducts / Q000096:biosynthesis*; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013662:Tea; D014018:Tissue Distribution