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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-4-26
pubmed:abstractText
Polymorphic glutathione S-transferase (GST) enzymes are involved in the metabolism of xenobiotics. They are of particular interest when studying disease susceptibility and adverse drug responses. The present work deals with the genetic polymorphisms and expression of the five GST classes (alpha, mu, pi, theta and zeta) in human lung and hepatocyte cell lines. We have determined their bioavailability for in vitro approaches. Common genetic polymorphisms of GSTM1 (*0, null), GSTT1 (*0) and GSTP1 (*A/*B, I105V) are detectable. The frequencies of the polymorphisms are within the expected range for a Caucasian population with one exception. The GSTM1*0 allele is 1.5-fold more frequent in lung cell lines. GST mRNAs are frequently but not uniformly distributed among unstimulated in vitro conditions. Lung cell lines show an approximately six-fold higher total GST transcript expression than hepatocyte cell lines. Additional GST transcripts have been identified for GSTT1; they represent alternative new splicing variants that occur in cancerous cell lines and in healthy lung tissue and blood. GST enzyme activity is mainly influenced by GSTP1. The activity promoted by 1-chloro-2,4-dinitrobenzene is significantly correlated to the GSTP1 mRNA expression level (R2=0.77, P<0.001). Individual human cell lines thus express GST isoenzymes in a similar pattern to human tissue. The most common genetic polymorphisms are present among the cell lines and have to be considered for in vitro stimulation approaches in a combinatory pattern.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0302-766X
pubmed:author
pubmed:issnType
Print
pubmed:volume
324
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-32
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Expression patterns and novel splicing variants of glutathione-S-transferase isoenzymes of human lung and hepatocyte cell lines.
pubmed:affiliation
Department of Human Exposure Research and Epidemiology, UFZ - Centre for Environmental Research Leipzig-Halle, Permoserstrasse 15, 04318 Leipzig, Germany. mario.bauer@ufz.de
pubmed:publicationType
Journal Article