Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China; Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, Kawasaki, Japan; Department of Environmental, Occupational Health and Toxicology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, Kawasaki, Japan.
Toxicol In Vitro. 2020 Aug;66:104880. doi: 10.1016/j.tiv.2020.104880. Epub 2020 May 5.
Recently, it was reported that ten cases of bladder cancer occurred among employees, who handled several kinds of aromatic amines, at a Japanese chemical plant. The common aromatic amines were identified as ortho-toluidine, para-toluidine, aniline, ortho-chloroaniline, ortho-anisidine, and 2,4-dimethylaniline. All of these aromatic amines, except ortho-chloroaniline, have been found to be carcinogenic in animals and/or humans. Genotoxic events are known to be crucial steps in the initiation of cancer; information on the genotoxicity of these aromatic amines is insufficient and consistent results have not been obtained. In this study, we examined the genotoxicity of the six different aromatic amines associated with bladder cancer by assessing phosphorylated histone H2AX (γ-H2AX) in a cultured human urothelial cell line, 1T1. We showed that all six aromatic amines generated γ-H2AX. In addition, the γ-H2AX-inducing potential of these six aromatic amines was distinctly different; ortho-chloroaniline and 2,4-dimethylaniline showed particularly high potential, followed by ortho-toluidine, ortho-anisidine, para-toluidine ≒ aniline. The findings of this study may provide important information for the risk assessment of chemicals and for interpreting epidemiological studies on occupational bladder cancer.
最近，有报道称在一家日本化工厂，有 10 名接触多种芳香胺的员工患上膀胱癌。常见的芳香胺被鉴定为邻甲苯胺、对甲苯胺、苯胺、邻氯苯胺、邻茴香胺和 2,4-二甲基苯胺。除邻氯苯胺外，所有这些芳香胺在动物和/或人类中均被发现具有致癌性。遗传毒性事件被认为是癌症发生的关键步骤；这些芳香胺的遗传毒性信息不足，且未得出一致的结果。在这项研究中，我们通过评估培养的人尿路上皮细胞系 1T1 中的磷酸化组蛋白 H2AX（γ-H2AX），检测了与膀胱癌相关的六种不同芳香胺的遗传毒性。结果表明，这六种芳香胺均可产生 γ-H2AX。此外，这六种芳香胺诱导 γ-H2AX 的能力明显不同；邻氯苯胺和 2,4-二甲基苯胺表现出特别高的潜力，其次是邻甲苯胺、邻茴香胺、对甲苯胺≈苯胺。本研究的结果可为化学品风险评估以及对职业性膀胱癌的流行病学研究提供重要信息。
