Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2

Mao Wen Weng, Yi Min Hsiao, Hui Ling Chiou, Shun Fa Yang, Yih Shou Hsieh, Ya Wen Cheng, Chieh Hsiang Yang, Jiunn Liang Ko

研究成果: 雜誌貢獻文章同行評審

16 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)493-502
頁數10
期刊DNA Repair
4
發行號4
DOIs
出版狀態已發佈 - 四月 4 2005
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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