绿茶抑制大鼠体内杂环胺-DNA加合物的形成

食物中的致突变物２－氨基－１－甲基－６－苯基咪唑并「４，５－ｂ」吡啶可诱发大鼠结肠和乳腺肿瘤，而且与人类癌症特别是结肠和直肠癌的密切关系。本研究以致癌物－ＤＮＡ加合物为生物标记物，观察绿茶对ＰｈＩＰ致癌作用的预防效果及机理。

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. CONCLUSION: 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.