Investigation of organic solvent-mediated carcinogenic mechanisms of bile duct cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670073
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: TAKADA Tappei 東京大学, 医学部附属病院, 講師 (90376468)
• Co-Investigator(Kenkyū-buntansha): TOYODA Yu 東京大学, 医学部附属病院, 特任助教 (80650340)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 胆汁排泄 / トランスポーター / 胆管側膜輸送体

Outline of Final Research Achievements

Some young employees who had a long history of exposure to halogenated hydrocarbon solvents, composed mostly of 1,2-dichloropropane, developed occupational cholangiocarcinoma. Although this dihaloalkane has been used in various industrial fields, there has been no biological evidence explaining the cholangiocarcinoma latency, as well as little understanding of general cholangiocarcinoma risk. In the present study, we explored the biliary excretion of 1,2-DCP metabolites by an untargeted metabolomics approach and the related molecular mechanisms with in vitro and in vivo experiments. We found that 1,2-DCP was conjugated with glutathione in the liver, and that the glutathione-conjugated forms of 1,2-DCP, including a potential carcinogen that contains a chloride atom, were excreted into bile by the bile canalicular membrane transporter, ABCC2. Our findings would contribute to uncover the latent mechanism by which the chronic exposure to 1,2-DCP increases cholangiocarcinoma risk.

Free Research Field

医療系薬学