绿茶抑制大鼠体内杂环胺-DNA加合物的形成

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

目的食物中的致突变物２氨基１甲基６苯基咪唑并［４，５ｂ］吡啶（ＰｈＩＰ）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有密切关系。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。方法雄性ＳＤ大鼠分别饮水或饮茶（３％）１０天后，经口摄入ＰｈＩＰ（１０ｍｇ／ｋｇ）。以３２Ｐ后标记方法测定动物心、肝、肺和结肠ＰｈＩＰＤＮＡ加合物，同时以１氯２，４二硝基苯为底物测定肝、肺和结肠粘膜细胞液谷胱甘肽硫转移酶（ＧＳＴ）活性。结果大鼠摄入ＰｈＩＰ后上述器官中均有ＰｈＩＰＤＮＡ加合物形成，含量（加合物／１０８核苷）以结肠粘膜最高（５３±９），其次为心（４１±１４）和肺（２２±５），而肝中含量很低（５±３）。动物饮茶１０天后给予致癌物，各器官中的ＰｈＩＰＤＮＡ加合物含量显著低于对照组，抑制率达５９％～６６％（Ｐ＜０．０１）。饮茶不影响上述组织中ＧＳＴ活性水平，提示饮茶抑制ＰｈＩＰＤＮＡ加合物形成与总ＧＳＴ活性无关。结论饮茶可有效抑制大鼠体内ＰｈＩＰＤＮＡ加合物形成。因为致癌物ＤＮＡ加合物形成是化学致癌过程所必需的起始事件，所以饮茶可预防ＰｈＩＰ潜?

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 colorcctal 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 32 P 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 consurnption of green tea may have significant impact in chemoprevontion against human cancer presumably related to PhIP and other heterocyclie amines.