Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
1,2-Dichloropropane (1,2-DCP) was used in the offset colour proof printing. In 2017, IARC reclassified it from Group 3 to Group 1, due to an outbreak of cholangiocarcinoma (CCA) among workers in Japan, who used 1,2 -DCP in their work. 1,2-DCP-induced (occupational) CCA in comparison with other forms of CCA, showed an early onset, accompanied by extensive pre-cancerous lesions in bile ducts. The exact mechanisms leading to occupational CCA remains poorly understood. The study investigated the molecular mechanisms of occupational CCA using human immortalized cholangiocytes MMNK-1 cells and human leukemia-derived THP-1 monocytes.
Following treatment of 100-800μM 1,2-DCP to either monocultured MMNK-1 cells or co-culture of MMNK-1/differentiated THP-1 macrophages for 24 hours, cell viability was assessed using MTS assay. LDH cytotoxicity assay and measurement of ROS production using DCFDA assay were performed.
Results show increased production of ROS in the MMNK-1/THP-1 co-cultured cells compared with monocultured MMNK-1 cells. Cell proliferation was increased in monocultured MMNK-1 cells exposed to 1,2-DCP but not co-cultured MMNK-1/differentiated THP-1 macrophages. There was an increased level of LDH cytotoxicity in co-cultured MMNK-1/differentiated THP-1 macrophages exposed to 1,2-DCP but not monocultured MMNK-1 cells.
The results demonstrated that exposure to 1,2-DCP enhances ROS production in human cholangiocytes co-cultured with macrophages, being accompanied by increase in cytotoxicity. The production of ROS might be a key mechanism involved in the 1,2-DCP-induced CCA.
