Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes
Abstract 1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing wo...
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| Veröffentlicht in: | Toxicological sciences 2018-04, Vol.162 (2), p.559-569 |
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| creator | Zhang, Xiao Zong, Cai Zhang, Lingyi Garner, Edwin Sugie, Shigeyuki Huang, Chinyen Wu, Wenting Chang, Jie Sakurai, Toshihiro Kato, Masashi Ichihara, Sahoko Kumagai, Shinji Ichihara, Gaku |
| description | Abstract
1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450. |
| doi_str_mv | 10.1093/toxsci/kfx272 |
| format | Article |
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1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfx272</identifier><identifier>PMID: 29228347</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Animals ; Apoptosis - drug effects ; Bile Ducts - drug effects ; Bile Ducts - enzymology ; Bile Ducts - pathology ; Carcinogens, Environmental - toxicity ; Cell Proliferation - drug effects ; Cytochrome P-450 Enzyme Inhibitors - pharmacology ; Cytochrome P-450 Enzyme System - metabolism ; Inhalation Exposure ; Liver - drug effects ; Liver - enzymology ; Liver - pathology ; Lung - drug effects ; Lung - enzymology ; Lung - pathology ; Male ; Mice, Inbred C57BL ; Propane - analogs & derivatives ; Propane - toxicity</subject><ispartof>Toxicological sciences, 2018-04, Vol.162 (2), p.559-569</ispartof><rights>The Author(s) 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-7d9c7ac131c253f635fcc9b7c81c0da14a53833853edafe9d8516d210164fa2b3</citedby><cites>FETCH-LOGICAL-c515t-7d9c7ac131c253f635fcc9b7c81c0da14a53833853edafe9d8516d210164fa2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29228347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiao</creatorcontrib><creatorcontrib>Zong, Cai</creatorcontrib><creatorcontrib>Zhang, Lingyi</creatorcontrib><creatorcontrib>Garner, Edwin</creatorcontrib><creatorcontrib>Sugie, Shigeyuki</creatorcontrib><creatorcontrib>Huang, Chinyen</creatorcontrib><creatorcontrib>Wu, Wenting</creatorcontrib><creatorcontrib>Chang, Jie</creatorcontrib><creatorcontrib>Sakurai, Toshihiro</creatorcontrib><creatorcontrib>Kato, Masashi</creatorcontrib><creatorcontrib>Ichihara, Sahoko</creatorcontrib><creatorcontrib>Kumagai, Shinji</creatorcontrib><creatorcontrib>Ichihara, Gaku</creatorcontrib><title>Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Abstract
1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Bile Ducts - drug effects</subject><subject>Bile Ducts - enzymology</subject><subject>Bile Ducts - pathology</subject><subject>Carcinogens, Environmental - toxicity</subject><subject>Cell Proliferation - drug effects</subject><subject>Cytochrome P-450 Enzyme Inhibitors - pharmacology</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Inhalation Exposure</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - pathology</subject><subject>Lung - drug effects</subject><subject>Lung - enzymology</subject><subject>Lung - pathology</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Propane - analogs & derivatives</subject><subject>Propane - toxicity</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkLtOwzAUQC0EoqUwsiKPDIT6ESfxWKXlIRXRAQamyPWDGlI7shOp_XtSpbAiXeleXR2d4QBwjdE9RpxOW7-L0k6_zY7k5ASM-2eWIE746fHOUIFG4CLGL4QwzhA_ByPCCSlomo-BW-waH7ugoTfwxUoNWw_xHUnmVm5qH3zTj3AaPjvVSR1h-bFKGUrmutFOadfCVfC1NTqI1noHhVNw1vim9dHGg7Pc-Fq4T-vlvtXxEpwZUUd9ddwT8P6weCufkuXr43M5WyaSYdYmueIyFxJTLAmjJqPMSMnXuSywRErgVDBaUFowqpUwmquC4UwRjHCWGkHWdAKSwSuDjzFoUzXBbkXYVxhVh27V0K0auvX8zcA33Xqr1R_9G6oHbgfAd80_rh-vKno4</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Zhang, Xiao</creator><creator>Zong, Cai</creator><creator>Zhang, Lingyi</creator><creator>Garner, Edwin</creator><creator>Sugie, Shigeyuki</creator><creator>Huang, Chinyen</creator><creator>Wu, Wenting</creator><creator>Chang, Jie</creator><creator>Sakurai, Toshihiro</creator><creator>Kato, Masashi</creator><creator>Ichihara, Sahoko</creator><creator>Kumagai, Shinji</creator><creator>Ichihara, Gaku</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20180401</creationdate><title>Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes</title><author>Zhang, Xiao ; Zong, Cai ; Zhang, Lingyi ; Garner, Edwin ; Sugie, Shigeyuki ; Huang, Chinyen ; Wu, Wenting ; Chang, Jie ; Sakurai, Toshihiro ; Kato, Masashi ; Ichihara, Sahoko ; Kumagai, Shinji ; Ichihara, Gaku</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-7d9c7ac131c253f635fcc9b7c81c0da14a53833853edafe9d8516d210164fa2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Bile Ducts - drug effects</topic><topic>Bile Ducts - enzymology</topic><topic>Bile Ducts - pathology</topic><topic>Carcinogens, Environmental - toxicity</topic><topic>Cell Proliferation - drug effects</topic><topic>Cytochrome P-450 Enzyme Inhibitors - pharmacology</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Inhalation Exposure</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - pathology</topic><topic>Lung - drug effects</topic><topic>Lung - enzymology</topic><topic>Lung - pathology</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Propane - analogs & derivatives</topic><topic>Propane - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xiao</creatorcontrib><creatorcontrib>Zong, Cai</creatorcontrib><creatorcontrib>Zhang, Lingyi</creatorcontrib><creatorcontrib>Garner, Edwin</creatorcontrib><creatorcontrib>Sugie, Shigeyuki</creatorcontrib><creatorcontrib>Huang, Chinyen</creatorcontrib><creatorcontrib>Wu, Wenting</creatorcontrib><creatorcontrib>Chang, Jie</creatorcontrib><creatorcontrib>Sakurai, Toshihiro</creatorcontrib><creatorcontrib>Kato, Masashi</creatorcontrib><creatorcontrib>Ichihara, Sahoko</creatorcontrib><creatorcontrib>Kumagai, Shinji</creatorcontrib><creatorcontrib>Ichihara, Gaku</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiao</au><au>Zong, Cai</au><au>Zhang, Lingyi</au><au>Garner, Edwin</au><au>Sugie, Shigeyuki</au><au>Huang, Chinyen</au><au>Wu, Wenting</au><au>Chang, Jie</au><au>Sakurai, Toshihiro</au><au>Kato, Masashi</au><au>Ichihara, Sahoko</au><au>Kumagai, Shinji</au><au>Ichihara, Gaku</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>162</volume><issue>2</issue><spage>559</spage><epage>569</epage><pages>559-569</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>Abstract
1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>29228347</pmid><doi>10.1093/toxsci/kfx272</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Toxicological sciences, 2018-04, Vol.162 (2), p.559-569 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis - drug effects Bile Ducts - drug effects Bile Ducts - enzymology Bile Ducts - pathology Carcinogens, Environmental - toxicity Cell Proliferation - drug effects Cytochrome P-450 Enzyme Inhibitors - pharmacology Cytochrome P-450 Enzyme System - metabolism Inhalation Exposure Liver - drug effects Liver - enzymology Liver - pathology Lung - drug effects Lung - enzymology Lung - pathology Male Mice, Inbred C57BL Propane - analogs & derivatives Propane - toxicity |
| title | Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes |
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