Document Detail


Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2.
MedLine Citation:
PMID:  15725629     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular detoxification is important for the routine removal of environmental and dietary carcinogens. Glutathione S-transferases (GST) are major cellular phase II detoxification enzymes. MRC-5 cells have been found to exhibit significantly higher GST activity than human H1355 cells. This study investigates whether GST-M2 activity acts as a critical determinant of the target dose of carcinogenic benzo[a]pyrene-diolepoxide (BPDE) and whether it has an effect on MDM2 splicing in the two cell lines. We used RT-PCR to clone Mu-class GST cDNA. Two forms of GST coming from the cell lines were characterized as GST-M2 (from MRC-5 cells) and GST-M4 (from H1355 cells). Nested-PCR showed that BPDE-induced MDM2 splicing had occurred in the H1355 cell line but not in normal MRC-5 cells. Furthermore, using nested-PCR and competitive ELISA, we found that in H1355 cells modified to stably overexpress GST-M2, splicing was abolished and BPDE adducts appeared in low abundance. In conclusion, exogenously overexpressed GST-M2 was effective in reducing BPDE-induced DNA damage in H1355 cells. The catalytic activity of GST-M2 may play an important future role in lowering the incidence of BPDE-induced DNA damage.
Authors:
Mao-Wen Weng; Yi-Min Hsiao; Hui-Ling Chiou; Shun-Fa Yang; Yih-Shou Hsieh; Ya-Wen Cheng; Chieh-Hsiang Yang; Jiunn-Liang Ko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-19
Journal Detail:
Title:  DNA repair     Volume:  4     ISSN:  1568-7864     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-02-23     Completed Date:  2005-08-08     Revised Date:  2007-05-12    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  493-502     Citation Subset:  IM    
Affiliation:
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan 40203, ROC.
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MeSH Terms
Descriptor/Qualifier:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
Base Sequence
Cell Line, Tumor
DNA Adducts
DNA Damage / drug effects*
DNA Primers
Enzyme-Linked Immunosorbent Assay
Glutathione Transferase / genetics*,  metabolism
Humans
Isoenzymes / genetics*,  metabolism
Kinetics
Lung Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/DNA Adducts; 0/DNA Primers; 0/Isoenzymes; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; EC 2.5.1.18/Glutathione Transferase; EC 2.5.1.18/glutathione S-transferase Mu 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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