Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro
1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangio...
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MDPI AG
2021-06-01
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author | Abigail Ekuban Cai Zong Frederick Adams Ekuban Yusuke Kimura Ryoya Takizawa Kota Morikawa Kazuo Kinoshita Sahoko Ichihara Seiichiroh Ohsako Gaku Ichihara |
author_facet | Abigail Ekuban Cai Zong Frederick Adams Ekuban Yusuke Kimura Ryoya Takizawa Kota Morikawa Kazuo Kinoshita Sahoko Ichihara Seiichiroh Ohsako Gaku Ichihara |
author_sort | Abigail Ekuban |
collection | DOAJ |
description | 1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was diagnosed in a group of workers exposed to 1,2 -DCP in an offset color proof-printing company in Japan. In comparison with other forms of cholangiocarcinoma, 1,2-DCP-induced cholangiocarcinoma was of early onset and accompanied by extensive pre-cancerous lesions in large bile ducts. However, the mechanism of 1,2-DCP-induced cholangiocarcinoma is poorly understood. Inflammatory cell proliferation was observed in various sites of the bile duct in the noncancerous hepatic tissues of the 1,2-DCP-induced cholangiocarcinoma. The aim of this study was to enhance our understanding of the mechanism of 1,2-DCP-related cholangiocarcinogenesis. We applied an in vitro system to investigate the effects of 1,2-DCP, using MMNK-1 cholangiocytes cultured alone or with THP-1 macrophages. The cultured cells were exposed to 1,2-DCP at 0, 0.1, 0.2, 0.4, and 0.8 mM for 24 h, and then assessed for cell proliferation, cell cytotoxicity, DNA damage, and ROS production. Exposure to 1,2-DCP increased proliferation of MMNK-1 cholangiocytes cultured alone, but not those cultured with macrophages. 1,2-DCP also increased LDH cytotoxicity, DNA damage, and ROS production in MMNK-1 cholangiocytes co-cultured with macrophages but not those cultured alone. 1,2-DCP increased TNFα and IL-1β protein expression in macrophages. The results highlight the role of macrophages in enhancing the effects of 1,2-DCP on cytotoxicity, ROS production, and DNA damage in cholangiocytes. |
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language | English |
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spelling | doaj.art-2e6a2b9ee4c348f1a91318afbc6a2b522023-11-21T22:23:26ZengMDPI AGToxics2305-63042021-06-019612810.3390/toxics9060128Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In VitroAbigail Ekuban0Cai Zong1Frederick Adams Ekuban2Yusuke Kimura3Ryoya Takizawa4Kota Morikawa5Kazuo Kinoshita6Sahoko Ichihara7Seiichiroh Ohsako8Gaku Ichihara9Department of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, JapanEvolutionary Medicine, Shizuoka Graduate University of Public Health, Shizuoka 420-0881, JapanDepartment of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, JapanLaboratory of Environmental Health Sciences, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, JapanDepartment of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, Japan1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was diagnosed in a group of workers exposed to 1,2 -DCP in an offset color proof-printing company in Japan. In comparison with other forms of cholangiocarcinoma, 1,2-DCP-induced cholangiocarcinoma was of early onset and accompanied by extensive pre-cancerous lesions in large bile ducts. However, the mechanism of 1,2-DCP-induced cholangiocarcinoma is poorly understood. Inflammatory cell proliferation was observed in various sites of the bile duct in the noncancerous hepatic tissues of the 1,2-DCP-induced cholangiocarcinoma. The aim of this study was to enhance our understanding of the mechanism of 1,2-DCP-related cholangiocarcinogenesis. We applied an in vitro system to investigate the effects of 1,2-DCP, using MMNK-1 cholangiocytes cultured alone or with THP-1 macrophages. The cultured cells were exposed to 1,2-DCP at 0, 0.1, 0.2, 0.4, and 0.8 mM for 24 h, and then assessed for cell proliferation, cell cytotoxicity, DNA damage, and ROS production. Exposure to 1,2-DCP increased proliferation of MMNK-1 cholangiocytes cultured alone, but not those cultured with macrophages. 1,2-DCP also increased LDH cytotoxicity, DNA damage, and ROS production in MMNK-1 cholangiocytes co-cultured with macrophages but not those cultured alone. 1,2-DCP increased TNFα and IL-1β protein expression in macrophages. The results highlight the role of macrophages in enhancing the effects of 1,2-DCP on cytotoxicity, ROS production, and DNA damage in cholangiocytes.https://www.mdpi.com/2305-6304/9/6/1281,2-Dichloropropanecytotoxicitycholangiocarcinomachemical carcinogenesiswork safetycarcinogenic compounds |
spellingShingle | Abigail Ekuban Cai Zong Frederick Adams Ekuban Yusuke Kimura Ryoya Takizawa Kota Morikawa Kazuo Kinoshita Sahoko Ichihara Seiichiroh Ohsako Gaku Ichihara Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro Toxics 1,2-Dichloropropane cytotoxicity cholangiocarcinoma chemical carcinogenesis work safety carcinogenic compounds |
title | Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro |
title_full | Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro |
title_fullStr | Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro |
title_full_unstemmed | Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro |
title_short | Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro |
title_sort | role of macrophages in cytotoxicity reactive oxygen species production and dna damage in 1 2 dichloropropane exposed human cholangiocytes in vitro |
topic | 1,2-Dichloropropane cytotoxicity cholangiocarcinoma chemical carcinogenesis work safety carcinogenic compounds |
url | https://www.mdpi.com/2305-6304/9/6/128 |
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