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通过氧化应激抑制剂调节饮用水消毒副产物碘乙酸的细胞毒性和遗传毒性。

Modulation of the cytotoxicity and genotoxicity of the drinking water disinfection byproduct lodoacetic acid by suppressors of oxidative stress.

作者信息

Cemeli Eduardo, Wagner Elizabeth D, Anderson Diana, Richardson Susan D, Plewa Michael J

机构信息

Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.

出版信息

Environ Sci Technol. 2006 Mar 15;40(6):1878-83. doi: 10.1021/es051602r.

Abstract

Drinking water disinfection byproducts (DBPs) are generated by the chemical disinfection of water and may pose a hazard to the public health. Previously we demonstrated that iodoacetic acid was the most cytotoxic and genotoxic DBP analyzed in a mammalian cell system. Little is known of the mechanisms of its genotoxicity. The involvement of oxidative stress in the toxicity of iodoacetic acid was analyzed with the antioxidants catalase and butylated hydroxyanisole (BHA). lodoacetic acid toxicity was quantitatively measured with and without antioxidants in Salmonella typhimurium strain TA100 and with Chinese hamster ovary (CHO) cells. The endpoints included cytotoxicity in S. typhimurium or in CHO cells, mutagenicity in S. typhimurium, and genotoxicity in CHO cells. Neither catalase nor BHA reduced the level of iodoacetic acid induced cytotoxicity in S. typhimurium. In CHO cells neither antioxidant caused a significant reduction in iodoacetic acid induced cytotoxicity. However, in S. typhimurium, BHA or catalase reduced the mutagenicity of iodoacetic acid by 33.5 and 26.8%, respectively. Likewise, BHA or catalase reduced iodoacetic acid induced genomic DNA damage by 86.5 and 42%, respectively. These results support the hypothesis that oxidative stress is involved in the induction of genotoxicity and mutagenicity by iodoacetic acid.

摘要

饮用水消毒副产物(DBPs)是通过水的化学消毒产生的,可能对公众健康构成危害。此前我们证明,在哺乳动物细胞系统中分析的碘乙酸是细胞毒性和遗传毒性最强的消毒副产物。对其遗传毒性机制知之甚少。我们用抗氧化剂过氧化氢酶和丁基羟基茴香醚(BHA)分析了氧化应激在碘乙酸毒性中的作用。在鼠伤寒沙门氏菌TA100菌株和中国仓鼠卵巢(CHO)细胞中,分别在有和没有抗氧化剂的情况下对碘乙酸毒性进行了定量测定。检测终点包括鼠伤寒沙门氏菌或CHO细胞中的细胞毒性、鼠伤寒沙门氏菌中的致突变性以及CHO细胞中的遗传毒性。过氧化氢酶和BHA均未降低碘乙酸在鼠伤寒沙门氏菌中诱导的细胞毒性水平。在CHO细胞中,两种抗氧化剂均未显著降低碘乙酸诱导的细胞毒性。然而,在鼠伤寒沙门氏菌中,BHA和过氧化氢酶分别使碘乙酸的致突变性降低了33.5%和26.8%。同样,BHA和过氧化氢酶分别使碘乙酸诱导的基因组DNA损伤降低了86.5%和42%。这些结果支持了氧化应激参与碘乙酸诱导的遗传毒性和致突变性这一假说。

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