Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP
Background/Methods: N-nitroso-bis(2-oxopropyl)amine (BOP) induces pancreatic ductal adenocarcinoma in Syrian golden hamsters, but not in rats or mice. To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellula...
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| Veröffentlicht in: | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2002-01, Vol.2 (6), p.519-527 |
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| container_title | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] |
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| creator | Ulrich, Alexis B. Standop, Jens Schmied, Bruno M. Schneider, Matthias B. Lawson, Terence A. Pour, Parviz M. |
| description | Background/Methods: N-nitroso-bis(2-oxopropyl)amine (BOP) induces pancreatic ductal adenocarcinoma in Syrian golden hamsters, but not in rats or mice. To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellular expression of nine cytochrome P-450 isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, and CYP3A4) and of three glutathione S-transferase isozymes (GST-π, GST-α, and GST-μ) was investigated in the pancreas of hamsters, rats, and mice by immunohis-tochemistry. Results: We found a wide species variation in the presence and cellular localization of the enzymes and a lack of several enzymes, including GST-a in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with ham- ster and mouse. Conclusion: Although the results could not clarify the reasons for the species differences in the pancreatic carcinogenicity of BOP, the presence of most of the cytochrome P-450 isozymes in pancreatic islets of all three species highlights the important role of the islets in drug metabolism. |
| doi_str_mv | 10.1159/000066094 |
| format | Article |
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To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellular expression of nine cytochrome P-450 isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, and CYP3A4) and of three glutathione S-transferase isozymes (GST-π, GST-α, and GST-μ) was investigated in the pancreas of hamsters, rats, and mice by immunohis-tochemistry. Results: We found a wide species variation in the presence and cellular localization of the enzymes and a lack of several enzymes, including GST-a in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with ham- ster and mouse. Conclusion: Although the results could not clarify the reasons for the species differences in the pancreatic carcinogenicity of BOP, the presence of most of the cytochrome P-450 isozymes in pancreatic islets of all three species highlights the important role of the islets in drug metabolism.</description><identifier>ISSN: 1424-3903</identifier><identifier>EISSN: 1424-3911</identifier><identifier>DOI: 10.1159/000066094</identifier><identifier>PMID: 12435864</identifier><language>eng</language><publisher>Basel, Switzerland: Elsevier B.V</publisher><subject>Animals ; Aryl Hydrocarbon Hydroxylases ; BOP ; Carcinogens - metabolism ; Carcinogens - pharmacology ; Cricetinae - metabolism ; Cytochrome P-450 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - metabolism ; Drug-metabolizing enzymes ; Glutathione S-transferase ; Glutathione Transferase - metabolism ; Hamster ; Islets ; Islets of Langerhans - enzymology ; Isoenzymes - metabolism ; Male ; Mesocricetus ; Mice - metabolism ; Mice, Nude ; Mouse ; Nitrosamines - metabolism ; Nitrosamines - pharmacology ; Original Paper ; Pancreas ; Pancreas - drug effects ; Pancreas - enzymology ; Rat ; Rats - metabolism ; Rats, Wistar ; Species Specificity ; Tissue Distribution</subject><ispartof>Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 2002-01, Vol.2 (6), p.519-527</ispartof><rights>2002 IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd.</rights><rights>2002 S. Karger AG, Basel and IAP</rights><rights>Copyright 2002 S. Karger AG, Basel and IAP</rights><rights>Copyright (c) 2002 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-acfb6a572764f200fdd8972c7163151fee06a1691b8c62a879747422a9970c43</citedby><cites>FETCH-LOGICAL-c465t-acfb6a572764f200fdd8972c7163151fee06a1691b8c62a879747422a9970c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2430,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12435864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ulrich, Alexis B.</creatorcontrib><creatorcontrib>Standop, Jens</creatorcontrib><creatorcontrib>Schmied, Bruno M.</creatorcontrib><creatorcontrib>Schneider, Matthias B.</creatorcontrib><creatorcontrib>Lawson, Terence A.</creatorcontrib><creatorcontrib>Pour, Parviz M.</creatorcontrib><title>Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP</title><title>Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]</title><addtitle>Pancreatology</addtitle><description>Background/Methods: N-nitroso-bis(2-oxopropyl)amine (BOP) induces pancreatic ductal adenocarcinoma in Syrian golden hamsters, but not in rats or mice. To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellular expression of nine cytochrome P-450 isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, and CYP3A4) and of three glutathione S-transferase isozymes (GST-π, GST-α, and GST-μ) was investigated in the pancreas of hamsters, rats, and mice by immunohis-tochemistry. Results: We found a wide species variation in the presence and cellular localization of the enzymes and a lack of several enzymes, including GST-a in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with ham- ster and mouse. Conclusion: Although the results could not clarify the reasons for the species differences in the pancreatic carcinogenicity of BOP, the presence of most of the cytochrome P-450 isozymes in pancreatic islets of all three species highlights the important role of the islets in drug metabolism.</description><subject>Animals</subject><subject>Aryl Hydrocarbon Hydroxylases</subject><subject>BOP</subject><subject>Carcinogens - metabolism</subject><subject>Carcinogens - pharmacology</subject><subject>Cricetinae - metabolism</subject><subject>Cytochrome P-450</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Drug-metabolizing enzymes</subject><subject>Glutathione S-transferase</subject><subject>Glutathione Transferase - metabolism</subject><subject>Hamster</subject><subject>Islets</subject><subject>Islets of Langerhans - enzymology</subject><subject>Isoenzymes - metabolism</subject><subject>Male</subject><subject>Mesocricetus</subject><subject>Mice - metabolism</subject><subject>Mice, Nude</subject><subject>Mouse</subject><subject>Nitrosamines - metabolism</subject><subject>Nitrosamines - pharmacology</subject><subject>Original Paper</subject><subject>Pancreas</subject><subject>Pancreas - drug effects</subject><subject>Pancreas - enzymology</subject><subject>Rat</subject><subject>Rats - metabolism</subject><subject>Rats, Wistar</subject><subject>Species Specificity</subject><subject>Tissue Distribution</subject><issn>1424-3903</issn><issn>1424-3911</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0EFPHCEYBmDS1FRre-jZxBBvTXZaYBhmOFpjWxNTPXifsPCxojswBcZ0_Rv9w2W76-pBLpDwfC_kRegTJV8obeRXUpYQRPI36IByxqtaUvp2dyb1Pnqf0h0hjFEq36F9ynjddIIfoL_nf8YIKbngcbDYxGlRDZDVPCzdo_MLDP5xNUDCzuN8C3hUXkdQaY1v1ZAyxBkewpRghpU3OKo8wyVwDN6sx42zFiL4vFzhHF5GZKexVlE7HxbgnXZ5tQ79dnX9Ae1ZtUzwcbsfopvv5zdnP6vLqx8XZ6eXleaiyZXSdi5U07JWcMsIscZ0smW6paKmDbUARCgqJJ13WjDVtbLlLWdMSdkSzetDdLKJHWP4PUHK_V2Yoi8v9owRWgoiXUGfN0jHkFIE24_RDSquekr6dfn9rvxij7eB03wA8yy3bRdwtAH3Ki4g7sDT-Mmrt9env_6DfjS2oHqDoBTz4ApL2oHXYFwEnXsT3Cs_-wd666VC</recordid><startdate>20020101</startdate><enddate>20020101</enddate><creator>Ulrich, Alexis B.</creator><creator>Standop, Jens</creator><creator>Schmied, Bruno M.</creator><creator>Schneider, Matthias B.</creator><creator>Lawson, Terence A.</creator><creator>Pour, Parviz M.</creator><general>Elsevier B.V</general><general>Elsevier Limited</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><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20020101</creationdate><title>Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP</title><author>Ulrich, Alexis B. ; Standop, Jens ; Schmied, Bruno M. ; Schneider, Matthias B. ; Lawson, Terence A. ; Pour, Parviz M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-acfb6a572764f200fdd8972c7163151fee06a1691b8c62a879747422a9970c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Aryl Hydrocarbon Hydroxylases</topic><topic>BOP</topic><topic>Carcinogens - metabolism</topic><topic>Carcinogens - pharmacology</topic><topic>Cricetinae - metabolism</topic><topic>Cytochrome P-450</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Drug-metabolizing enzymes</topic><topic>Glutathione S-transferase</topic><topic>Glutathione Transferase - metabolism</topic><topic>Hamster</topic><topic>Islets</topic><topic>Islets of Langerhans - enzymology</topic><topic>Isoenzymes - metabolism</topic><topic>Male</topic><topic>Mesocricetus</topic><topic>Mice - metabolism</topic><topic>Mice, Nude</topic><topic>Mouse</topic><topic>Nitrosamines - metabolism</topic><topic>Nitrosamines - pharmacology</topic><topic>Original Paper</topic><topic>Pancreas</topic><topic>Pancreas - drug effects</topic><topic>Pancreas - enzymology</topic><topic>Rat</topic><topic>Rats - metabolism</topic><topic>Rats, Wistar</topic><topic>Species Specificity</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ulrich, Alexis B.</creatorcontrib><creatorcontrib>Standop, Jens</creatorcontrib><creatorcontrib>Schmied, Bruno M.</creatorcontrib><creatorcontrib>Schneider, Matthias B.</creatorcontrib><creatorcontrib>Lawson, Terence A.</creatorcontrib><creatorcontrib>Pour, Parviz M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ulrich, Alexis B.</au><au>Standop, Jens</au><au>Schmied, Bruno M.</au><au>Schneider, Matthias B.</au><au>Lawson, Terence A.</au><au>Pour, Parviz M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP</atitle><jtitle>Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]</jtitle><addtitle>Pancreatology</addtitle><date>2002-01-01</date><risdate>2002</risdate><volume>2</volume><issue>6</issue><spage>519</spage><epage>527</epage><pages>519-527</pages><issn>1424-3903</issn><eissn>1424-3911</eissn><abstract>Background/Methods: N-nitroso-bis(2-oxopropyl)amine (BOP) induces pancreatic ductal adenocarcinoma in Syrian golden hamsters, but not in rats or mice. To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellular expression of nine cytochrome P-450 isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, and CYP3A4) and of three glutathione S-transferase isozymes (GST-π, GST-α, and GST-μ) was investigated in the pancreas of hamsters, rats, and mice by immunohis-tochemistry. Results: We found a wide species variation in the presence and cellular localization of the enzymes and a lack of several enzymes, including GST-a in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with ham- ster and mouse. Conclusion: Although the results could not clarify the reasons for the species differences in the pancreatic carcinogenicity of BOP, the presence of most of the cytochrome P-450 isozymes in pancreatic islets of all three species highlights the important role of the islets in drug metabolism.</abstract><cop>Basel, Switzerland</cop><pub>Elsevier B.V</pub><pmid>12435864</pmid><doi>10.1159/000066094</doi><tpages>9</tpages></addata></record> |
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| ispartof | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 2002-01, Vol.2 (6), p.519-527 |
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| language | eng |
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| source | Karger e-journals Complete Collection; MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Aryl Hydrocarbon Hydroxylases BOP Carcinogens - metabolism Carcinogens - pharmacology Cricetinae - metabolism Cytochrome P-450 Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - metabolism Drug-metabolizing enzymes Glutathione S-transferase Glutathione Transferase - metabolism Hamster Islets Islets of Langerhans - enzymology Isoenzymes - metabolism Male Mesocricetus Mice - metabolism Mice, Nude Mouse Nitrosamines - metabolism Nitrosamines - pharmacology Original Paper Pancreas Pancreas - drug effects Pancreas - enzymology Rat Rats - metabolism Rats, Wistar Species Specificity Tissue Distribution |
| title | Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP |
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