大白菜抑制大鼠体内致癌物PhIP-DNA加合物形成及其可能的作用机理

Chemoprevention of 2 amino 1 methyl 6 phenylimidazo pyridine induced carcinogen DNA adducts by Chinese cabbage in rats

目的研究大白菜（ｂｒａｓｓｉｃａｃｈｉｎｅｎｓｉｓ）对结肠致癌物２－氨基－１－甲基－６－苯基咪唑［４，５－ｂ］吡啶（ＰｈＩＰ）致癌的预防作用及机理。方法雄性ＳＤ大鼠喂饲基础饲料或掺有大白菜粉（２０％）混合饲料１０天后，经口摄入ＰｈＩＰ（１０ｍｇ／ｋｇ）。以３２Ｐ－后标记方法分析动物结肠粘膜、心、肺和肝中ＰｈＩＰ－ＤＮＡ加合物含量，并测定参与ＰｈＩＰ代谢的细胞色素Ｐ４５０（ＣＹＰ）１Ａ１和１Ａ２以及谷胱甘肽转硫酶（ＧＳＴ）活性。结果经喂饲含大白菜饲料的大鼠，其结肠、心、肺、肝等器官中，ＰｈＩＰ－ＤＮＡ加合物含量显著低于喂饲基础饲料的动物（Ｐ＜０．０１），抑制率结肠为８２．３％、心脏为６０．６％、肺为４８．４％、肝脏为４８．９％。大白菜对参与ＰｈＩＰ解毒的ＣＹＰ１Ａ１和ＧＳＴ有显著的诱导作用。与对照组比较，喂饲大白菜大鼠的肝ＣＹＰ１Ａ１活性增加８０．６％（Ｐ＜０．０１），肝和肺细胞浆ＧＳＴ活性分别增加１８．２％和３５．６％（Ｐ＜０．０５）。结论食用大白菜可有效抑制ＰｈＩＰ－ＤＮＡ加合物形成。

Objectives To examine the preventive effect of Chinese cabbage (Brassica chinensis) against colon carcinogen 2 amino 1 methyl 6 phenylimidazopyridine (PhIP) induced PhIP DNA adduct formation in rats and its possible mechanism. Methods Sprague Dawley rats were maintained for 10 days on lab chow or chow containing 20% (w/w) freeze dried cabbage powder prior to administration of a single dose of PhIP (10 mg/kg) 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. 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 (GST) towards CDNB in the liver, lung and colon mucosa 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 an inhibition rate of 82.3, 60.6, 48.4 and 48.9%, respectively ( P < 0.01). Enzyme assays revealed that both CYP1A1 and 1A2 were induced by cabbage, but the induction was preferential for CYP1A1 over 1A2 (80.6% vs 50.2%). GST activity towards CDNB in the liver and lung, but not colon, was also significantly induced by the cabbage. Conclusion The results indicate a preventive effect of Chinese cabbage against PhIP initiated carcinogenesis in rats and the mechanism is likely to involve induction of detoxification enzymes.