| pubmed-article:1632637 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0015576 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0038317 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0014939 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0010762 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0012203 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0030011 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0870883 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0007382 | lld:lifeskim |
| pubmed-article:1632637 | lifeskim:mentions | umls-concept:C0053241 | lld:lifeskim |
| pubmed-article:1632637 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:1632637 | pubmed:dateCreated | 1992-8-20 | lld:pubmed |
| pubmed-article:1632637 | pubmed:abstractText | Diethylstilbestrol (DES) or catecholestrogens are metabolized by microsomal enzymes to quinones, DES Q or catecholestrogen quinones, respectively, which have been shown to bind covalently to DNA and to undergo redox cycling. The isoforms of cytochrome P450 catalyzing this oxidation of estrogens to genotoxic intermediates were not known and have been identified in this study by (a) using microsomes of rats treated with various inducers of cytochrome P450; (b) using purified cytochrome P450 isoforms; and (c) examining the peroxide cofactor concentrations necessary for this oxidation by microsomes or pure isoenzymes. The highest rate of oxidation of DES to DES Q was obtained using beta-naphthoflavone-induced microsomes (14.0 nmol DES Q/mg protein/min) or cytochrome P450 IA1 (6.4 pmol DES Q/min/pmol P450). Isosafrole-induced microsomes or cytochrome P450 IA2 oxidized DES to quinone at one-third or one-fifth of that rate, respectively. Low or negligible rates of oxidation were measured when oxidations were catalyzed by microsomal rat liver enzymes induced by phenobarbital, ethanol, or pregnenolone-16 alpha-carbonitrile or by pure cytochromes P450 IIB1, IIB4, IIC3, IIC6, IIE1, IIE2, IIG1, or IIIA6. Cytochrome P450 IA1 also catalyzed the oxidation of 2- or 4-hydroxyestradiol to their corresponding quinones. The beta-naphthoflavone-induced microsomes and cytochrome P450 IA1 had the highest "affinity" for cumene hydroperoxide cofactor (Km = 77 microM). Cofactor concentrations above 250 microM resulted in decreased rates of oxidation. The other cytochrome P450 isoforms required much higher cofactor concentrations and were not inactivated at high cofactor concentrations. The data demonstrate that beta-naphthoflavone-inducible cytochrome P450 IA family enzymes catalyze most efficiently the oxidation of estrogenic hydroquinones to corresponding quinones. This oxidation may represent a detoxification pathway to keep organic hydroperoxides at minimal concentrations. The resulting quinone metabolites may be detoxified by other pathways. However, in cells with decreased detoxifying enzyme activities, quinones metabolites may accumulate and initiate carcinogenesis or cell death by covalent arylation of DNA or proteins. | lld:pubmed |
| pubmed-article:1632637 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:language | eng | lld:pubmed |
| pubmed-article:1632637 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1632637 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:1632637 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:1632637 | pubmed:issn | 0003-9861 | lld:pubmed |
| pubmed-article:1632637 | pubmed:author | pubmed-author:StrobelH WHW | lld:pubmed |
| pubmed-article:1632637 | pubmed:author | pubmed-author:RoyDD | lld:pubmed |
| pubmed-article:1632637 | pubmed:author | pubmed-author:LiehrJ GJG | lld:pubmed |
| pubmed-article:1632637 | pubmed:author | pubmed-author:BernhardtAA | lld:pubmed |
| pubmed-article:1632637 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:1632637 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:1632637 | pubmed:volume | 296 | lld:pubmed |
| pubmed-article:1632637 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:1632637 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:1632637 | pubmed:pagination | 450-6 | lld:pubmed |
| pubmed-article:1632637 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:1632637 | pubmed:meshHeading | pubmed-meshheading:1632637-... | lld:pubmed |
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| pubmed-article:1632637 | pubmed:meshHeading | pubmed-meshheading:1632637-... | lld:pubmed |
| pubmed-article:1632637 | pubmed:meshHeading | pubmed-meshheading:1632637-... | lld:pubmed |
| pubmed-article:1632637 | pubmed:meshHeading | pubmed-meshheading:1632637-... | lld:pubmed |
| pubmed-article:1632637 | pubmed:meshHeading | pubmed-meshheading:1632637-... | lld:pubmed |
| pubmed-article:1632637 | pubmed:year | 1992 | lld:pubmed |
| pubmed-article:1632637 | pubmed:articleTitle | Catalysis of the oxidation of steroid and stilbene estrogens to estrogen quinone metabolites by the beta-naphthoflavone-inducible cytochrome P450 IA family. | lld:pubmed |
| pubmed-article:1632637 | pubmed:affiliation | Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550-2782. | lld:pubmed |
| pubmed-article:1632637 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:1632637 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1632637 | lld:pubmed |
