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Metabolism of a Phenylarsenical in Human Hepatic Cells and Identification of a New Arsenic Metabolite
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.est.7b05081 Qingqing Liu 1 , Elaine M. Leslie 1, 2 , Birget Moe 1, 3 , Hongquan Zhang 1 , Donna N. Douglas 4 , Norman M. Kneteman 4 , X. Chris Le 1
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.est.7b05081 Qingqing Liu 1 , Elaine M. Leslie 1, 2 , Birget Moe 1, 3 , Hongquan Zhang 1 , Donna N. Douglas 4 , Norman M. Kneteman 4 , X. Chris Le 1
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Environmental contamination and human consumption of chickens could result in potential exposure to Roxarsone (3-nitro-4-hydroxyphenylarsonic acid), an organic arsenical that has been used as a chicken feed additive in many countries. However, little is known about the metabolism of Roxarsone in humans. The objective of this research was to investigate the metabolism of Roxarsone in human liver cells and to identify new arsenic metabolites of toxicological significance. Human primary hepatocytes and hepatocellular carcinoma HepG2 cells were treated with 20 or 100 μM Roxarsone. Arsenic species were characterized using a strategy of complementary chromatography and mass spectrometry. The results showed that Roxarsone was metabolized to more than 10 arsenic species in human hepatic cells. A new metabolite was identified as a thiolated Roxarsone. The 24 h IC50 values of thiolated Roxarsone for A549 lung cancer cells and T24 bladder cancer cells were 380 ± 80 and 42 ± 10 μM, respectively, more toxic than Roxarsone, whose 24 h IC50 values for A549 and T24 were 9300 ± 1600 and 6800 ± 740 μM, respectively. The identification and toxicological studies of the new arsenic metabolite are useful for understanding the fate of arsenic species and assessing the potential impact of human exposure to Roxarsone.
中文翻译：
苯砷在人肝细胞中的代谢和新砷代谢物的鉴定
环境污染和鸡肉的人类食用可能导致潜在暴露于Roxarsone（3-硝基-4-羟基苯基ar磺酸），Roxarsone（一种有机砷）已在许多国家用作鸡饲料添加剂。然而，关于罗沙松在人体内的代谢知之甚少。这项研究的目的是研究人肝细胞中罗沙酮的代谢，并确定具有毒理学意义的新砷代谢物。用20或100μM的Roxarsone处理人原代肝细胞和肝细胞癌HepG2细胞。使用互补色谱和质谱分析法对砷物质进行表征。结果表明，罗沙酮在人肝细胞中被代谢为10多种砷。一种新的代谢产物被鉴定为硫醇化的罗沙酮。硫醇化Roxarsone对A549肺癌细胞和T24膀胱癌细胞的50值分别为380±80和42±10μM，比Roxarsone毒性更高，后者对A549和T24的24 h IC 50值为9300±1600和6800±740分别为μM。新砷代谢物的鉴定和毒理学研究对于理解砷物种的命运以及评估人类暴露于Roxarsone的潜在影响是有用的。
更新日期：2018-01-17
中文翻译：
苯砷在人肝细胞中的代谢和新砷代谢物的鉴定
环境污染和鸡肉的人类食用可能导致潜在暴露于Roxarsone（3-硝基-4-羟基苯基ar磺酸），Roxarsone（一种有机砷）已在许多国家用作鸡饲料添加剂。然而，关于罗沙松在人体内的代谢知之甚少。这项研究的目的是研究人肝细胞中罗沙酮的代谢，并确定具有毒理学意义的新砷代谢物。用20或100μM的Roxarsone处理人原代肝细胞和肝细胞癌HepG2细胞。使用互补色谱和质谱分析法对砷物质进行表征。结果表明，罗沙酮在人肝细胞中被代谢为10多种砷。一种新的代谢产物被鉴定为硫醇化的罗沙酮。硫醇化Roxarsone对A549肺癌细胞和T24膀胱癌细胞的50值分别为380±80和42±10μM，比Roxarsone毒性更高，后者对A549和T24的24 h IC 50值为9300±1600和6800±740分别为μM。新砷代谢物的鉴定和毒理学研究对于理解砷物种的命运以及评估人类暴露于Roxarsone的潜在影响是有用的。
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