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Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase
Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen....
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| Published in: | Carcinogenesis (New York) 2003-10, Vol.24 (10), p.1695-1703 |
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| creator | Stiborová, Marie Frei, Eva Sopko, Bruno Sopková, Klára Marková, Vladimíra Laňková, Martina Kumstýřová, Tereza Wiessler, Manfred Schmeiser, Heinz H. |
| description | Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI–DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA–DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI–DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI–DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI–DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction. |
| doi_str_mv | 10.1093/carcin/bgg119 |
| format | article |
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Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI–DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA–DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI–DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI–DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI–DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction.</description><identifier>ISSN: 0143-3334</identifier><identifier>ISSN: 1460-2180</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgg119</identifier><identifier>PMID: 12869422</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>3-dioxolo-5-carboxylic acid ; 4-d)-1 ; 6-nitro-phenanthro- ; 7-(deoxyadenosin-N6-yl)aristolactam I ; 7-(deoxyadenosin-N6-yl)aristolactam II ; 7-(deoxyguanosin-N2-yl) aristolactam I ; 7-(deoxyguanosin-N2-yl) aristolactam II ; 8-methoxy-6-nitro-phenanthro- ; AAI ; AAII ; AAN ; Aldehyde Oxidase - metabolism ; Animals ; aristolochic acid ; aristolochic acid nephropathy ; Aristolochic Acids - chemistry ; Aristolochic Acids - metabolism ; Aristolochic Acids - pharmacokinetics ; Biological and medical sciences ; Biotransformation ; Carcinogenesis, carcinogens and anticarcinogens ; Carcinogens - chemistry ; Carcinogens - metabolism ; Carcinogens - pharmacokinetics ; Chemical agents ; Chromatography, High Pressure Liquid ; Cytosol - enzymology ; dA–AAI ; dA–AAII ; dG–AAI ; dG–AAII ; DNA Adducts - analysis ; Enzyme Inhibitors - metabolism ; Humans ; Kidney - enzymology ; Liver - enzymology ; Male ; Medical sciences ; Models, Molecular ; NAD(P)H Dehydrogenase (Quinone) - analysis ; NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors ; NAD(P)H Dehydrogenase (Quinone) - metabolism ; NAD(P)H:quinone oxidoreductase ; NQO1 ; polyethylenimine ; Rats ; Rats, Wistar ; Tumors ; xanthine oxidase ; Xanthine Oxidase - analysis ; Xanthine Oxidase - antagonists & inhibitors ; Xanthine Oxidase - metabolism</subject><ispartof>Carcinogenesis (New York), 2003-10, Vol.24 (10), p.1695-1703</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Oct 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-edf4f32af964adf317dd416b28e75e272f16aafcb4ec5057a9d5cf23465c8fbb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27937,27938</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15196162$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12869422$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stiborová, Marie</creatorcontrib><creatorcontrib>Frei, Eva</creatorcontrib><creatorcontrib>Sopko, Bruno</creatorcontrib><creatorcontrib>Sopková, Klára</creatorcontrib><creatorcontrib>Marková, Vladimíra</creatorcontrib><creatorcontrib>Laňková, Martina</creatorcontrib><creatorcontrib>Kumstýřová, Tereza</creatorcontrib><creatorcontrib>Wiessler, Manfred</creatorcontrib><creatorcontrib>Schmeiser, Heinz H.</creatorcontrib><title>Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI–DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA–DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI–DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI–DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI–DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction.</description><subject>3-dioxolo-5-carboxylic acid</subject><subject>4-d)-1</subject><subject>6-nitro-phenanthro-</subject><subject>7-(deoxyadenosin-N6-yl)aristolactam I</subject><subject>7-(deoxyadenosin-N6-yl)aristolactam II</subject><subject>7-(deoxyguanosin-N2-yl) aristolactam I</subject><subject>7-(deoxyguanosin-N2-yl) aristolactam II</subject><subject>8-methoxy-6-nitro-phenanthro-</subject><subject>AAI</subject><subject>AAII</subject><subject>AAN</subject><subject>Aldehyde Oxidase - metabolism</subject><subject>Animals</subject><subject>aristolochic acid</subject><subject>aristolochic acid nephropathy</subject><subject>Aristolochic Acids - chemistry</subject><subject>Aristolochic Acids - metabolism</subject><subject>Aristolochic Acids - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Carcinogens - chemistry</subject><subject>Carcinogens - metabolism</subject><subject>Carcinogens - pharmacokinetics</subject><subject>Chemical agents</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cytosol - enzymology</subject><subject>dA–AAI</subject><subject>dA–AAII</subject><subject>dG–AAI</subject><subject>dG–AAII</subject><subject>DNA Adducts - analysis</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Humans</subject><subject>Kidney - enzymology</subject><subject>Liver - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>NAD(P)H Dehydrogenase (Quinone) - analysis</subject><subject>NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors</subject><subject>NAD(P)H Dehydrogenase (Quinone) - metabolism</subject><subject>NAD(P)H:quinone oxidoreductase</subject><subject>NQO1</subject><subject>polyethylenimine</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Tumors</subject><subject>xanthine oxidase</subject><subject>Xanthine Oxidase - analysis</subject><subject>Xanthine Oxidase - antagonists & inhibitors</subject><subject>Xanthine Oxidase - metabolism</subject><issn>0143-3334</issn><issn>1460-2180</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpdkU1v1DAQhi0EokvhyBVZSCA4hPojcZLeqgW6VBUfEqCKi-XY412XxG7tZNXlH_EvyW5WLOI0I80z77yaF6GnlLyhpOYnWkXt_EmzXFJa30MzmguSMVqR-2hGaM4zznl-hB6ldE0IFbyoH6IjyipR54zN0O_F0CmP9aYPKbROY_C_Nh0k7Pw6tGswY4P7FeAOetXsCKV7t1a9Cx4Hi6f7YQl-O4ou9aENerXjnDnFsHYGvAZsQ8QRzLDdhn9Fmg1e7Ux8PHv76vPrxentMAp6wOHOmTCtqASP0QOr2gRP9vUYfXv_7ut8kV1-Ov8wP7vMdMFIn4GxueVM2VrkylhOS2NyKhpWQVkAK5mlQimrmxx0QYpS1abQlvFcFLqyTcOP0ctJ9yaG2wFSLzuXNLSt8hCGJGldVUTQagSf_wdehyH60ZtktOZlTaotlE2QjiGlCFbeRNepuJGUyG2AcnqgnAIc-Wd70aHpwBzofWIj8GIPqKRVa6Py2qUDV9BaUMEOh8dE4O7vXMWfUpS8LOTi6oe8uijO5_zLhfzO_wBDx7lt</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>Stiborová, Marie</creator><creator>Frei, Eva</creator><creator>Sopko, Bruno</creator><creator>Sopková, Klára</creator><creator>Marková, Vladimíra</creator><creator>Laňková, Martina</creator><creator>Kumstýřová, Tereza</creator><creator>Wiessler, Manfred</creator><creator>Schmeiser, Heinz H.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20031001</creationdate><title>Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase</title><author>Stiborová, Marie ; Frei, Eva ; Sopko, Bruno ; Sopková, Klára ; Marková, Vladimíra ; Laňková, Martina ; Kumstýřová, Tereza ; Wiessler, Manfred ; Schmeiser, Heinz H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-edf4f32af964adf317dd416b28e75e272f16aafcb4ec5057a9d5cf23465c8fbb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>3-dioxolo-5-carboxylic acid</topic><topic>4-d)-1</topic><topic>6-nitro-phenanthro-</topic><topic>7-(deoxyadenosin-N6-yl)aristolactam I</topic><topic>7-(deoxyadenosin-N6-yl)aristolactam II</topic><topic>7-(deoxyguanosin-N2-yl) aristolactam I</topic><topic>7-(deoxyguanosin-N2-yl) aristolactam II</topic><topic>8-methoxy-6-nitro-phenanthro-</topic><topic>AAI</topic><topic>AAII</topic><topic>AAN</topic><topic>Aldehyde Oxidase - metabolism</topic><topic>Animals</topic><topic>aristolochic acid</topic><topic>aristolochic acid nephropathy</topic><topic>Aristolochic Acids - chemistry</topic><topic>Aristolochic Acids - metabolism</topic><topic>Aristolochic Acids - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Carcinogens - chemistry</topic><topic>Carcinogens - metabolism</topic><topic>Carcinogens - pharmacokinetics</topic><topic>Chemical agents</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cytosol - enzymology</topic><topic>dA–AAI</topic><topic>dA–AAII</topic><topic>dG–AAI</topic><topic>dG–AAII</topic><topic>DNA Adducts - analysis</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Humans</topic><topic>Kidney - enzymology</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>NAD(P)H Dehydrogenase (Quinone) - analysis</topic><topic>NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors</topic><topic>NAD(P)H Dehydrogenase (Quinone) - metabolism</topic><topic>NAD(P)H:quinone oxidoreductase</topic><topic>NQO1</topic><topic>polyethylenimine</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Tumors</topic><topic>xanthine oxidase</topic><topic>Xanthine Oxidase - analysis</topic><topic>Xanthine Oxidase - antagonists & inhibitors</topic><topic>Xanthine Oxidase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stiborová, Marie</creatorcontrib><creatorcontrib>Frei, Eva</creatorcontrib><creatorcontrib>Sopko, Bruno</creatorcontrib><creatorcontrib>Sopková, Klára</creatorcontrib><creatorcontrib>Marková, Vladimíra</creatorcontrib><creatorcontrib>Laňková, Martina</creatorcontrib><creatorcontrib>Kumstýřová, Tereza</creatorcontrib><creatorcontrib>Wiessler, Manfred</creatorcontrib><creatorcontrib>Schmeiser, Heinz H.</creatorcontrib><collection>Istex</collection><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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stiborová, Marie</au><au>Frei, Eva</au><au>Sopko, Bruno</au><au>Sopková, Klára</au><au>Marková, Vladimíra</au><au>Laňková, Martina</au><au>Kumstýřová, Tereza</au><au>Wiessler, Manfred</au><au>Schmeiser, Heinz H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>24</volume><issue>10</issue><spage>1695</spage><epage>1703</epage><pages>1695-1703</pages><issn>0143-3334</issn><issn>1460-2180</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI–DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA–DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI–DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI–DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI–DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12869422</pmid><doi>10.1093/carcin/bgg119</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0143-3334 |
| ispartof | Carcinogenesis (New York), 2003-10, Vol.24 (10), p.1695-1703 |
| issn | 0143-3334 1460-2180 1460-2180 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19880618 |
| source | Oxford Journals |
| subjects | 3-dioxolo-5-carboxylic acid 4-d)-1 6-nitro-phenanthro- 7-(deoxyadenosin-N6-yl)aristolactam I 7-(deoxyadenosin-N6-yl)aristolactam II 7-(deoxyguanosin-N2-yl) aristolactam I 7-(deoxyguanosin-N2-yl) aristolactam II 8-methoxy-6-nitro-phenanthro- AAI AAII AAN Aldehyde Oxidase - metabolism Animals aristolochic acid aristolochic acid nephropathy Aristolochic Acids - chemistry Aristolochic Acids - metabolism Aristolochic Acids - pharmacokinetics Biological and medical sciences Biotransformation Carcinogenesis, carcinogens and anticarcinogens Carcinogens - chemistry Carcinogens - metabolism Carcinogens - pharmacokinetics Chemical agents Chromatography, High Pressure Liquid Cytosol - enzymology dA–AAI dA–AAII dG–AAI dG–AAII DNA Adducts - analysis Enzyme Inhibitors - metabolism Humans Kidney - enzymology Liver - enzymology Male Medical sciences Models, Molecular NAD(P)H Dehydrogenase (Quinone) - analysis NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors NAD(P)H Dehydrogenase (Quinone) - metabolism NAD(P)H:quinone oxidoreductase NQO1 polyethylenimine Rats Rats, Wistar Tumors xanthine oxidase Xanthine Oxidase - analysis Xanthine Oxidase - antagonists & inhibitors Xanthine Oxidase - metabolism |
| title | Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-11T10%3A06%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20cytosolic%20enzymes%20involved%20in%20the%20metabolic%20activation%20of%20carcinogenic%20aristolochic%20acid:%20evidence%20for%20reductive%20activation%20by%20human%20NAD(P)H:quinone%20oxidoreductase&rft.jtitle=Carcinogenesis%20(New%20York)&rft.au=Stiborova%CC%81,%20Marie&rft.date=2003-10-01&rft.volume=24&rft.issue=10&rft.spage=1695&rft.epage=1703&rft.pages=1695-1703&rft.issn=0143-3334&rft.eissn=1460-2180&rft.coden=CRNGDP&rft_id=info:doi/10.1093/carcin/bgg119&rft_dat=%3Cproquest_cross%3E423549981%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c520t-edf4f32af964adf317dd416b28e75e272f16aafcb4ec5057a9d5cf23465c8fbb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=219379088&rft_id=info:pmid/12869422&rfr_iscdi=true |