HepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen
The human hepatoma cell line, HepG2, retains many cellular functions often lost by cells in culture. This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1993-01, Vol.190 (1), p.15-19 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Roe, A.L. Snawder, J.E. Benson, R.W. Roberts, D.W. Casciano, D.A. |
| description | The human hepatoma cell line, HepG2, retains many cellular functions often lost by cells in culture. This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low levels of acetaminophen bioactivation, P450 IIE1 activity, and P450 IA1-IA2 activity were demonstrated in non-induced HepG2 microsomes. Acetone increased acetaminophen bioactivation and IIE1-dependent metabolism but not P450 IA1-IA2-dependent activity. Thus, HepG2 cells may provide an in vitro model for assessing human xenobiotic metabolism of acetaminophen and other drugs. |
| doi_str_mv | 10.1006/bbrc.1993.1003 |
| format | Article |
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This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low levels of acetaminophen bioactivation, P450 IIE1 activity, and P450 IA1-IA2 activity were demonstrated in non-induced HepG2 microsomes. Acetone increased acetaminophen bioactivation and IIE1-dependent metabolism but not P450 IA1-IA2-dependent activity. Thus, HepG2 cells may provide an in vitro model for assessing human xenobiotic metabolism of acetaminophen and other drugs.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.1993.1003</identifier><identifier>PMID: 8380689</identifier><identifier>CODEN: BBRCA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>acetaminophen ; Acetaminophen - metabolism ; Acetone - pharmacology ; Analytical, structural and metabolic biochemistry ; biochemical characteristics ; Biological and medical sciences ; Biotransformation ; Carcinoma, Hepatocellular ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP2E1 ; Cytochrome P-450 Enzyme System - metabolism ; cytochrome P450 ; endoplasmic reticulum ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. Psychology ; hepatoma ; Humans ; Liver Neoplasms ; man ; metabolism ; Microsomes - drug effects ; Microsomes - enzymology ; Mixed Function Oxygenases - metabolism ; Oxidoreductases ; Oxidoreductases - metabolism ; Oxidoreductases, N-Demethylating - metabolism ; Tumor Cells, Cultured</subject><ispartof>Biochemical and biophysical research communications, 1993-01, Vol.190 (1), p.15-19</ispartof><rights>1993 Academic Press</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-ca2566b78eb085e51f965521202aa6410ba900c20c5f8365f57c8f6311e907fe3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.1993.1003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4573769$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8380689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Roe, A.L.</creatorcontrib><creatorcontrib>Snawder, J.E.</creatorcontrib><creatorcontrib>Benson, R.W.</creatorcontrib><creatorcontrib>Roberts, D.W.</creatorcontrib><creatorcontrib>Casciano, D.A.</creatorcontrib><title>HepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The human hepatoma cell line, HepG2, retains many cellular functions often lost by cells in culture. This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low levels of acetaminophen bioactivation, P450 IIE1 activity, and P450 IA1-IA2 activity were demonstrated in non-induced HepG2 microsomes. Acetone increased acetaminophen bioactivation and IIE1-dependent metabolism but not P450 IA1-IA2-dependent activity. Thus, HepG2 cells may provide an in vitro model for assessing human xenobiotic metabolism of acetaminophen and other drugs.</description><subject>acetaminophen</subject><subject>Acetaminophen - metabolism</subject><subject>Acetone - pharmacology</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>biochemical characteristics</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Carcinoma, Hepatocellular</subject><subject>Cytochrome P-450 CYP1A1</subject><subject>Cytochrome P-450 CYP2E1</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>cytochrome P450</subject><subject>endoplasmic reticulum</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>hepatoma</subject><subject>Humans</subject><subject>Liver Neoplasms</subject><subject>man</subject><subject>metabolism</subject><subject>Microsomes - drug effects</subject><subject>Microsomes - enzymology</subject><subject>Mixed Function Oxygenases - metabolism</subject><subject>Oxidoreductases</subject><subject>Oxidoreductases - metabolism</subject><subject>Oxidoreductases, N-Demethylating - metabolism</subject><subject>Tumor Cells, Cultured</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv1DAQRi0EKkvhyg3JB8QtyziOHZvbagstUlf0QCtuluOMhVFiBztbiX9Pol31hjiNPs2b0cwj5C2DLQOQH7suuy3Tmq-RPyMbBhqqmkHznGxgIapasx8vyatSfgEw1kh9QS4UVyCV3pDDDU7XNd3jMJRPdBdpiPQhzDnRQ-pxoD5letcIqK5wwthjnOkBZ9ulIZSRJk93boljiGn6ifE1eeHtUPDNuV6S-y-fv-9vqttv11_3u9vKcdbMlbO1kLJrFXagBArmtRSiZjXU1sqGQWc1gKvBCa-4FF60TnnJGUMNrUd-ST6c9k45_T5imc0Yilt-sBHTsZhWiEZy3v4XZLJRrWJqAbcn0OVUSkZvphxGm_8YBmYVbVbRZhW9Rr4MvDtvPnYj9k_42ezSf3_u2-Ls4LONLpQnrBEtb-WKqROGi67HgNkUFzA67ENGN5s-hX9d8Be4SpXx</recordid><startdate>19930115</startdate><enddate>19930115</enddate><creator>Roe, A.L.</creator><creator>Snawder, J.E.</creator><creator>Benson, R.W.</creator><creator>Roberts, D.W.</creator><creator>Casciano, D.A.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19930115</creationdate><title>HepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen</title><author>Roe, A.L. ; Snawder, J.E. ; Benson, R.W. ; Roberts, D.W. ; Casciano, D.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-ca2566b78eb085e51f965521202aa6410ba900c20c5f8365f57c8f6311e907fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>acetaminophen</topic><topic>Acetaminophen - metabolism</topic><topic>Acetone - pharmacology</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>biochemical characteristics</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Carcinoma, Hepatocellular</topic><topic>Cytochrome P-450 CYP1A1</topic><topic>Cytochrome P-450 CYP2E1</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>cytochrome P450</topic><topic>endoplasmic reticulum</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>hepatoma</topic><topic>Humans</topic><topic>Liver Neoplasms</topic><topic>man</topic><topic>metabolism</topic><topic>Microsomes - drug effects</topic><topic>Microsomes - enzymology</topic><topic>Mixed Function Oxygenases - metabolism</topic><topic>Oxidoreductases</topic><topic>Oxidoreductases - metabolism</topic><topic>Oxidoreductases, N-Demethylating - metabolism</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roe, A.L.</creatorcontrib><creatorcontrib>Snawder, J.E.</creatorcontrib><creatorcontrib>Benson, R.W.</creatorcontrib><creatorcontrib>Roberts, D.W.</creatorcontrib><creatorcontrib>Casciano, D.A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roe, A.L.</au><au>Snawder, J.E.</au><au>Benson, R.W.</au><au>Roberts, D.W.</au><au>Casciano, D.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1993-01-15</date><risdate>1993</risdate><volume>190</volume><issue>1</issue><spage>15</spage><epage>19</epage><pages>15-19</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><coden>BBRCA9</coden><abstract>The human hepatoma cell line, HepG2, retains many cellular functions often lost by cells in culture. This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low levels of acetaminophen bioactivation, P450 IIE1 activity, and P450 IA1-IA2 activity were demonstrated in non-induced HepG2 microsomes. Acetone increased acetaminophen bioactivation and IIE1-dependent metabolism but not P450 IA1-IA2-dependent activity. Thus, HepG2 cells may provide an in vitro model for assessing human xenobiotic metabolism of acetaminophen and other drugs.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>8380689</pmid><doi>10.1006/bbrc.1993.1003</doi><tpages>5</tpages></addata></record> |
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| subjects | acetaminophen Acetaminophen - metabolism Acetone - pharmacology Analytical, structural and metabolic biochemistry biochemical characteristics Biological and medical sciences Biotransformation Carcinoma, Hepatocellular Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP2E1 Cytochrome P-450 Enzyme System - metabolism cytochrome P450 endoplasmic reticulum Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology hepatoma Humans Liver Neoplasms man metabolism Microsomes - drug effects Microsomes - enzymology Mixed Function Oxygenases - metabolism Oxidoreductases Oxidoreductases - metabolism Oxidoreductases, N-Demethylating - metabolism Tumor Cells, Cultured |
| title | HepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen |
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