Linked Life Data

10631125

Source:http://linkedlifedata.com/resource/pubmed/id/10631125

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-2-17
pubmed:abstractText
UDP-glucuronosyltransferase 1A7 (UGT1A7) is a polyaromatic hydrocarbon (PAH)-inducible UGT with activity toward various benzo[a]pyrene (B[a]P) metabolites. To investigate the influence of rat UGT1A7 on B[a]P-induced cytotoxicity, human lymphoblastoid L3 cells were transfected with pMF6 (control expression vector), p167Dtk2 (microsomal epoxide hydrolase expression vector), or p167Dtk2-1A7 (epoxide hydrolase/UGT1A7 coexpression vector), and the cell populations were compared for sensitivity to B[a]P-induced effects. B[a]P inhibited cell proliferation and decreased relative cell survival of p167Dtk2 and p167Dtk2-1A7 cells to a similar extent. Metabolism studies using [(3)H]B[a]P revealed increased formation of glucuronide conjugates of B[a]P-4,5-diol, 3-OH-, or 9-OH-B[a]P and an unidentified metabolite by p167Dtk2-1A7 cells, but the presence of unconjugated metabolites suggested that glucuronidation capacity may be limited. No differences between p167Dtk2 and p167Dtk2-1A7 L3 cells were observed in the growth inhibitory effects of 3-OH-B[a]P or B[a]P-7,8-diol, but p167Dtk2-1A7-expressing cells were found to be less sensitive to B[a]P-3,6-quinone-induced effects on cell proliferation and relative cell survival. The effect was also observed in AHH-1 lymphoblastoid cells expressing UGT1A7 without epoxide hydrolase. The UGT1A7-expressing AHH-1 cells were also less sensitive to growth inhibition by B[a]P-1,6-quinone and B[a]P-6,12-quinone. Flow cytometric analysis of vehicle and B[a]P-3, 6-quinone-exposed cell populations showed an association between UGT1A7 expression and resistance to B[a]P-3,6-quinone-induced apoptosis and loss of cell viability. These data suggest that UGT1A7 may be preferentially active toward B[a]P-quinones and that UGT1A7 may represent the PAH-inducible UGT activity previously implicated in protection against toxic redox cycling by B[a]P-3,6-quinone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10631125-Animals, pubmed-meshheading:10631125-Apoptosis, pubmed-meshheading:10631125-Benzo(a)pyrene, pubmed-meshheading:10631125-Benzopyrenes, pubmed-meshheading:10631125-Blotting, Western, pubmed-meshheading:10631125-Cell Division, pubmed-meshheading:10631125-Cell Line, pubmed-meshheading:10631125-Cell Survival, pubmed-meshheading:10631125-Chromatography, High Pressure Liquid, pubmed-meshheading:10631125-Drug Interactions, pubmed-meshheading:10631125-Epoxide Hydrolases, pubmed-meshheading:10631125-Flow Cytometry, pubmed-meshheading:10631125-Genetic Vectors, pubmed-meshheading:10631125-Glucuronides, pubmed-meshheading:10631125-Glucuronosyltransferase, pubmed-meshheading:10631125-Herpesvirus 4, Human, pubmed-meshheading:10631125-Humans, pubmed-meshheading:10631125-Lymphocytes, pubmed-meshheading:10631125-Rats, pubmed-meshheading:10631125-Transfection
pubmed:year
2000
pubmed:articleTitle
Differential protection by rat UDP-glucuronosyltransferase 1A7 against Benzo[a]pyrene-3,6-quinone- versus Benzo[a]pyrene-induced cytotoxic effects in human lymphoblastoid cells.
pubmed:affiliation
Department of Pharmacology and Toxicology, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA.
pubmed:publicationType
Journal Article, Comparative Study