Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta , 10-102 Clinical Sciences Building, Edmonton, Alberta, Canada T6G 2G3.
Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta , 7-08A Medical Sciences Building, Edmonton, Alberta, Canada T6G 2H7.
Environ Sci Technol. 2018 Feb 6;52(3):1386-1392. doi: 10.1021/acs.est.7b05081. Epub 2018 Jan 17.
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 IC 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 IC 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.
环境污染物和人类对鸡肉的消费可能导致潜在的罗沙砷（3-硝基-4-羟基苯胂酸）暴露，罗沙砷曾作为一种有机胂化合物被许多国家用作鸡饲料添加剂。然而，人们对罗沙砷在人体内的代谢知之甚少。本研究旨在研究罗沙砷在人肝细胞中的代谢情况，并鉴定具有毒理学意义的新砷代谢物。用人原代肝细胞和肝癌 HepG2 细胞分别用 20 或 100 μM 的罗沙砷处理。采用互补色谱和质谱联用策略对砷形态进行了表征。结果表明，罗沙砷在人肝细胞中代谢为 10 多种砷形态。鉴定出一种新的含硫罗沙砷代谢物。含硫罗沙砷对 A549 肺癌细胞和 T24 膀胱癌细胞的 24 h IC 值分别为 380 ± 80 和 42 ± 10 μM，比罗沙砷的毒性更大，其对 A549 和 T24 的 24 h IC 值分别为 9300 ± 1600 和 6800 ± 740 μM。对新砷代谢物的鉴定和毒理学研究有助于了解砷形态的命运，并评估人类接触罗沙砷的潜在影响。
