Linked Life Data

8221964

Source:http://linkedlifedata.com/resource/pubmed/id/8221964

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-12-7
pubmed:abstractText
Dihydrodiol dehydrogenase(s) (DD) have been implicated in the detoxication of proximate (trans-dihydrodiol) and ultimate carcinogenic (anti-diol-epoxide) metabolites of polycyclic aromatic hydrocarbons (PAHs). These activities are catalyzed by soluble hydroxysteroid dehydrogenases and/or by aldehyde reductases. Molecular cloning indicates tha these enzymes have a high degree of sequence identity with members of the aldo-keto reductase super family. Substrate specificity studies indicate that non-K-region trans-dihydrodiols are the preferred substrates and that anti-dio-epoxides are not oxidized by the enzyme. The products of the DD reaction are transient catechols which auto-oxidize to PAH-o-quinones. As a consequence of this auto-oxidation superoxide anion, hydrogen peroxide and semiquinone radicals are generated. Studies on the biotransformation of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene indicate that in subcellular fractions from uninduced rat liver, DD plays a significant role in the metabolism of this proximate carcinogen. Thus, the formation of benzo[a]pyrene-7,8-dione is only superseded by the formation of tetraols which are derived from the anti-diol epoxide of benzo[a]pyrene [anti-BPDE;(+/-)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene]. PAH-o-quinones produced by DD can inactivate the enzyme. These PAH-o-quinones also vary in their reactivity towards cellular nucleophiles, their cytotoxicity and their genotoxicity. Non-bay region and methylated bay-region PAH-o-quinones generated by DD are the most reactive Michael acceptors, and are also the most cytotoxic in hepatoma cells. Cytotoxicity results from the 1e- redox-cycling of the PAH-o-quinone, concomittant production of superoxide anion and a subsequent alteration in redoxstate. PAH-o-quinones are also genotoxic thus [3H]-benzo[a]pyrene-7,8-dione readily forms deoxyguanosine-adducts with native calf-thymus DNA, i.e., to the same extent as anti-BPDE. The cytotoxic and genotoxic properties of PAH-o-quinones suggest that DD may initiate a hitherto unrecognized pathway of PAH activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Dihydrodiol dehydrogenase and its role in polycyclic aromatic hydrocarbon metabolism.
pubmed:affiliation
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review