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首页> 外文期刊>Environmental Science & Technology >Potent Clastogenicity of Bisphenol Compounds in Mammalian Cells-Human CYP1A1 Being a Major Activating Enzyme
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Potent Clastogenicity of Bisphenol Compounds in Mammalian Cells-Human CYP1A1 Being a Major Activating Enzyme

机译：哺乳动物细胞中双酚化合物的有效含量 - 人CYP1A1是主要活化酶

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摘要

Bisphenols (BPs) are environmental pollutants with relevant DNA damage in human population; however, they are generally inactive in standard mutagenicity assays, possibly due to insufficient metabolic activation. In this study, induction of micronuclei and double-strand DNA breaks by BPA, BPF, and BPS in Chinese hamster V79-derived cell lines expressing various human CYP enzymes and a human hepatoma (C3A) (metabolism-proficient) cell line were investigated. Molecular docking of BPs to human CYPs indicated some substrate-enzyme potentials, including CYP1A1 for each compound, which did not induce micronuclei in V79-derived cell lines expressing human CYP1A2, 2E1, or 3A4 but became positive in human CYP1A1-expressing (V79-hCYP1A1) cells. In V79-hCYPlAl and C3A cells, all compounds induced double-strand DNA breaks and micronuclei formation, which were blocked/ significantly attenuated by 1-aminobenzotriazole (CYP inhibitor) or 7-hydroxyflavone (selective CYP1A1 inhibitor). Coexposure of C3A cells to pentachlorophenol (sulfotransferase 1 inhibitor) or ketoconazole (UDP-glucuronosyltransferase 1A inhibitor) potentiated micronuclei induction by each compound, with thresholds lowered from 2.5-5.0 to 0.6-1.2 μM. Immunofluorescence staining of centromere protein B with micronuclei formed in C3A cells by each compound indicated pure clastogenic effects. In conclusion, BPs are potently clastogenic in mammalian cells, which require activation primarily by human CYP1A1 and are negatively modulated by phase Ⅱ metabolism.
机译：双酚（BPS）是人口中具有相关DNA损伤的环境污染物;然而，它们在标准致突变性测定中通常是无活性的，可能是由于代谢活化不充分。在该研究中，在表达各种人CYP酶的中国仓鼠V79衍生的细胞系中BPA，BPF和BPS诱导微核和双链DNA断裂和表达各种人类CYP酶的细胞系（C3A）（代谢性易碎）细胞系。将BPS对人Cyps的分子对接表明了一些基质 - 酶电位，包括每个化合物的CYP1A1，其在表达人CYP1A2,2E1或3A4的V79衍生的细胞系中没有诱导微核，但在人CYP1A1的表达中变为阳性（V79- hcyp1a1）细胞。在V79-H形胞和C3A细胞中，所有化合物诱导双链DNA断裂和微核形成，其被1-氨基苯并二唑（CYP抑制剂）或7-羟基噻吩（选择性CYP1A1抑制剂）堵塞/显着衰减。 C3A细胞的群至五氯苯酚（磺基转移酶1抑制剂）或酮烷唑（UDP-葡糖醛糖基三转移酶1A抑制剂）各种化合物的增强的微核感应，阈值从2.5-5.0降低至0.6-1.2μm。通过各种化合物在C3A细胞中形成的微核B中的离心蛋白B的免疫荧光染色表明纯的抗纤溶作用。总之，BPS在哺乳动物细胞中具有纯粹的裂殖性，这需要主要由人CYP1A1激活，并且通过Ⅱ期代谢进行负面调节。

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  • 来源
    《Environmental Science & Technology》 |2020年第23期|15267-15276|共10页
  • 作者

    Hang Yu; Zhihong Chen; Keqi Hu; Zongying Yang; Meiqi Song; Zihuan Li; Yungang Liu;

  • 作者单位

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

    Department of Toxicology School of Public Health Southern Medical University Guangzhou 510515 China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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