1,2-Dichloropropane induces γ-H2AX expression in human cholangiocytes only in the presence of macrophages

Ryoya Takizawa, Sahoko Ichihara, Cai Zong, Kazuo Kinoshita, Toshihiro Sakurai, Akihiko Ikegami, Nathan Mise, Gaku Ichihara

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1 Citation (Scopus)


Recent epidemiological studies reported cases of cholangiocarcinoma in workers exposed to 1,2-dichloropropane (1,2-DCP) in an offset proof printing factory in Japan. The present study investigated the effects of 1,2-DCP on the expression of histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX), a marker of DNA double strand break, in human immortalized cholangiocytes MMNK-1 cells. Mono-cultures of MMNK-1 cells and co-cultures of MMNK-1 cells with THP-1 macrophages were exposed to 1,2-DCP at concentrations of 100 and 500 μM for 24 h. Expression of γ-H2AX was visualized by immunofluorescence staining. Exposure to 1,2-DCP had no effect on the expression of γ-H2AX in mono-cultured MMNK-1 cells, but significantly increased the number of nuclear foci stained by γ-H2AX in MMNK-1 cells co-cultured with THP-1 macrophages. Exposure to 1,2-DCP also significantly increased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in co-cultured MMNK-1 cells. The results suggest that macrophages play a critical role by producing cytokines in 1,2-DCP-induced DNA double strand break in MMNK-1 cells.

Original languageEnglish
Pages (from-to)134-144
Number of pages11
JournalToxicology Letters
Publication statusPublished - 1 Oct 2021


  • 1,2-Dichloropapane
  • Cholangiocytes
  • Cytokines
  • DNA double strand break
  • γ-H2AX


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