Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Toxicol Sci. 2018 Apr 1;162(2):559-569. doi: 10.1093/toxsci/kfx272.
1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450.
1,2-二氯丙烷（1,2-DCP）曾被用作工业上的脱漆剂。最近，国际癌症研究机构根据日本胶印工接触 1,2-DCP 后发生胆管癌的流行病学研究，将这种化合物重新分类为 1 组（对人类致癌）。为期两年的啮齿动物致癌性生物测定表明，1,2-DCP 可诱导肝脏和肺部肿瘤，但不诱导胆管肿瘤。本研究旨在评估 1,2-DCP 对小鼠胆管增殖和凋亡的毒性作用，以及细胞色素 P450（CYP450）在任何此类作用中的作用。雄性 C57BL/6JJcl 小鼠接受或不接受细胞色素 P450 抑制剂 1-氨基苯并三唑（1-ABT）的共同处理，并单独或联合暴露于 0、50 或 250ppm 的 1,2-DCP 或 0、50、250 或 1250ppm 的 1,2-DCP 8 小时/天，共 4 周。暴露于 1,2-DCP 可增加胆管细胞的增殖和凋亡，并导致严重的肝损伤，但对肺部没有影响。1-ABT 的共同处理消除了 1,2-DCP 对胆管细胞增殖和凋亡的影响。结果表明，1,2-DCP 可诱导胆管细胞增殖和凋亡，这种作用是通过 CYP450 介导的。
