Makena Patrudu S, Chung King-Thom
Department of Biology, The University of Memphis, TN 38152, United States.
Food Chem Toxicol. 2007 Oct;45(10):1899-909. doi: 10.1016/j.fct.2007.04.007. Epub 2007 Apr 21.
Benzidine (Bz), a human bladder carcinogen, was strongly mutagenic to Salmonella TA102 tester strain in the Ames Salmonella microsome/mutagenicity assay in the presence of rat liver S9 mix. Various non-mutagenic plant polyphenols were included in the assay to test their inhibitory effects on the Bz-induced mutations. Coumestrol, ellagic acid (EA), (-)-epicatechin (EC), (-)-epichatechingallate (ECG), gallic acid (GA), (-)-gallocatechin (GC), plumbagin, propyl gallate (PG), taxifolin, and 2,2',4'-trihydroxychalcone were found to have a strong inhibitory effect on Bz-induced mutations. (-)-Epigallo-catechingallate (EGCG), fisetin, (-)-gallocatechingallate (GCG), and piceatannol were moderately inhibitory to the mutations; whereas, (-)-catechin, (-)-catechingallate (CG), and reseveratrol were weakly inhibitory to the mutations. (-)-Epigallocatechin (EGC) and 7,3',4'-trihydroxy isoflavon were not inhibitory to the Bz-induced mutations. Isoliquirtigenin, quercetin dihydrate, and rhein were found to be mutagenic in tester strain TA102. Benzidine mediated lipid peroxidation was conducted employing the thiobarbituric acid reactive substances (TBARS) assay using linoleic acid as a substrate. In the presence of rat liver S9 mix, Bz could cause lipid peroxidation as an outcome of production of oxygen free radicals. Incorporation of the above mentioned non-mutagenic plant polyphenols significantly inhibited benzidine mediated lipid peroxidation in a time dependent manner. These polyphenols also effectively reduced the iron mediated lipid peroxidation. Thus, it is concluded that the inhibition of oxidative mutagenicity of Bz by plant polyphenols could be due to an inhibitory effect of plant polyphenols on the bioactivating enzymes such as cytochrome P-450 and peroxidase and the chelation of iron present in the cytochrome P-450 in the S9 mix. Thus, these plant polyphenols play a significant inhibitory role on Bz-induced mutagenicity.
联苯胺（Bz）是一种人类膀胱致癌物，在艾姆斯沙门氏菌微粒体/致突变性试验中，在存在大鼠肝脏S9混合物的情况下，对沙门氏菌TA102测试菌株具有强烈的致突变性。试验中纳入了各种非致突变性植物多酚，以测试它们对Bz诱导突变的抑制作用。发现香豆雌酚、鞣花酸（EA）、（-）-表儿茶素（EC）、（-）-表儿茶素没食子酸酯（ECG）、没食子酸（GA）、（-）-没食子儿茶素（GC）、白花丹素、没食子酸丙酯（PG）、 taxifolin和2,2',4'-三羟基查耳酮对Bz诱导的突变有强烈的抑制作用。（-）-表没食子儿茶素没食子酸酯（EGCG）、漆黄素、（-）-没食子儿茶素没食子酸酯（GCG）和白皮杉醇对突变有中等程度的抑制作用；而（-）-儿茶素、（-）-儿茶素没食子酸酯（CG）和白藜芦醇对突变有微弱的抑制作用。（-）-表没食子儿茶素（EGC）和7,3',4'-三羟基异黄酮对Bz诱导突变无抑制作用。发现异甘草素、二水槲皮素和大黄酸在测试菌株TA102中具有致突变性。采用以亚油酸为底物的硫代巴比妥酸反应物质（TBARS）试验进行联苯胺介导的脂质过氧化。在存在大鼠肝脏S9混合物的情况下，Bz可因产生氧自由基而导致脂质过氧化。上述非致突变性植物多酚的加入以时间依赖性方式显著抑制了联苯胺介导的脂质过氧化。这些多酚还有效降低了铁介导的脂质过氧化。因此，可以得出结论，植物多酚对联苯胺氧化致突变性的抑制可能是由于植物多酚对细胞色素P-450和过氧化物酶等生物活化酶的抑制作用以及对S9混合物中细胞色素P-450中铁的螯合作用。因此，这些植物多酚对Bz诱导的致突变性起显著的抑制作用。
