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Molecular mechanisms of aromatic amine-induced reactive oxygen species-mediated genotoxicity.

机译：芳香胺诱导的活性氧介导的遗传毒性的分子机制。

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摘要

We studied aromatic amine mediated production and genotoxicity of reactive oxygen species (ROS) employing Ames Salmonella/microsome mutagenicity assay using TA102 tester strain, thobarbituric acid reactive substance (TBARS) assay for lipidperoxidation. 4-Aminobiphenyl (4-Ab), benzidine (Bz) and some of the benzidine congeners were mutagenic on TA102 in the presence of S9. 4, 4'-Dinitro-2-biphenylamine was mutagenic to TA102 in the absence of S9. Incorporation of antioxidants and metal chelators such as superoxide dismutase (SOD), catalase (CAT), butylated hydroxytolune (BHT), and ethylenediaminetetraacetate (EDTA) into the test system decreased the mutagenicity of 4-Ab and Bz. Both 4-Ab and Bz induced lipidperoxidation in time dependent manner in TBARS assay.; We investigated the possibility of iron (II) and NADPH generating system (NGS) mediated oxidation of Bz and 4-Ab to produce ROS employing Ames Salmonella/microsome mutagenicity assay using TA98, TA100, and TA102 tester strains, and thobarbituric acid reactive substance (TBARS) assay to test lipidperoxidation. We also evaluated the possibility of DNA strand breaks using double stranded circular plasmid DNA employing agarose gel electrophoresis. Both Bz and 4-Ab were mutagenic in all the three tester strains and also induced lipidperoxidation in the presence of iron (II) and NGS and in the absence of S9. Incorporation of SOD, CAT, EDTA and desferroxamine (DF) (an iron chelator) not only decreased the mutagenicity of Bz and 4-Ab but also significantly inhibited the lipidperoxidation induced by Bz and 4-Ab. Both Bz and 4-Ab induced DNA strand breaks in the presence of iron (II).; To evaluate the antimutagenic effect of various dietary plant polyphenols on Bz-induced mutations and lipidperoxidation, we have incorporated various dietary polyphenols in combination with Bz into Ames assay using TA102 tester strain and also in TBARS assay. The plant polyphenols were categorized according to their antimutagenic effect on Bz-induced mutagencity and lipidperoxidation into "strongly, moderately, weakly inhibitory, and not inhibitory" (see chapter-5). Isoliquirtigenin, quercetin dihydrate and rhein were found to be mutagenic in tester strain TA102.; In conclusion, both Bz and 4-Ab could produce ROS and thus not only induce mutations in Salmonella tester strains and also cause lipidperoxidation in the presence of S9, or iron and NGS.
机译：我们研究了芳香族胺介导的活性氧物质（ROS）的产生和遗传毒性，方法是使用A102沙门氏菌/微粒体诱变测定法（使用TA102测试菌株），巴比妥酸活性物质（TBARS）测定脂质过氧化作用。在存在S9的条件下，TA102对4-氨基联苯（4-Ab），联苯胺（Bz）和某些联苯胺同源物有诱变作用。在不存在S9的情况下，4,4'-二硝基-2-联苯胺对TA102致突变。将抗氧化剂和金属螯合剂（例如超氧化物歧化酶（SOD），过氧化氢酶（CAT），丁基化羟基甲苯（BHT）和乙二胺四乙酸酯（EDTA））掺入测试系统会降低4-Ab和Bz的致突变性。在TBARS测定中4-Ab和Bz均以时间依赖性方式诱导脂质过氧化。我们研究了铁（II）和NADPH生成系统（NGS）介导的Bz和4-Ab氧化产生ROS的可能性，方法是使用TA98，TA100和TA102测试菌株和艾滋酸巴比妥酸反应物，通过埃姆氏沙门氏菌/微粒体诱变试验（TBARS）测定法测试脂质过氧化作用。我们还使用琼脂糖凝胶电泳评估了使用双链环状质粒DNA断裂DNA链的可能性。在所有三个测试菌株中，Bz和4-Ab都是诱变的，并且在铁（II）和NGS存在且不存在S9的情况下还诱导脂质过氧化。 SOD，CAT，EDTA和去铁胺（DF）（铁螯合剂）的结合不仅降低了Bz和4-Ab的致突变性，而且还显着抑制了Bz和4-Ab诱导的脂质过氧化。在铁（II）存在下，Bz和4-Ab诱导的DNA链断裂。为了评估各种膳食植物多酚对Bz诱导的突变和脂质过氧化的抗诱变作用，我们已将多种膳食多酚与Bz的混合物掺入了使用TA102测试菌株的Ames分析和TBARS分析中。根据植物多酚对Bz诱变和脂质过氧化的抗突变作用，将其分为“强，中，弱抑制和非抑制”（请参阅​​第5章）。在测试菌株TA102中发现异麦芽香皂苷元，二水槲皮素和大黄酸是诱变的。总之，Bz和4-Ab均可产生ROS，因此不仅在沙门氏菌测试菌株中诱导突变，而且在S9或铁和NGS存在下引起脂质过氧化。

著录项

  • 作者

    Makena, Suryanarayana Patrudu.;

  • 作者单位

    The University of Memphis.;

  • 授予单位 The University of Memphis.;
  • 学科 Biology Molecular.; Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 145 p.
  • 总页数 145
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;微生物学;
  • 关键词

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