Exposure of human cholangiocytes to 1,2-dichloropropane in the presence of macrophages induces base-excision repair-related genes in vitro

1,2-dichloropropane (1,2-DCP), a synthetic organic solvent, has been implicated in causality of cholangiocarcinoma. 1,2-DCP from Group 3 to Group 1. 1,2-DCP-induced occupational cholangiocarcinoma show a different carcinogenic process compared to common cholangiocarcinoma. However, the mechanism of 1,2-DCP induced carcinogenicity in cholangiocytes remains elusive. We reported previously that exposure of MMNK-1 cholangiocytes co-cultured with THP-1 macrophages, but not monocultured MMNK-1 cholangiocytes to 1,2-DCP induced activation-induced cytidine deaminase (AID) expression, DNA damage and ROS production. The aim of this study was to identify relevant biological processes or target genes expressed in response to 1,2-DCP, using an in vitro system where cholangiocytes are co-cultured with macrophages. The co-cultured cells were exposed to 1,2-DCP at 0, 0.1, and 0.4 mM for 24 hours and the cell lysates, assessed by transcriptome analysis. 1,2-DCP upregulated the expression of base excision repair genes in MMNK-1 cholangiocytes in the co-cultures, whereas it upregulated the expression of cell cycle-related genes in THP-1 macrophages. Activation of the base excision repair pathway might result from the previously observed DNA damage in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages. Cross talk interactions between cholangiocytes and macrophages could explain the observed increase in DNA damage in the cholangiocytes.