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

Mao W. Weng, Yi M. Hsiao, Hui Ling Chiou, Shun F. Yang, Yih Shou Hsieh, Ya W. Cheng, Chieh Hsiang Yang, Jiunn Liang Ko

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Abstract

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.

Original languageEnglish
Pages (from-to)493-502
Number of pages10
JournalDNA Repair
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 4 2005
Externally publishedYes

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Keywords

  • BPDE adduct
  • DNA damage
  • GST-M2
  • MDM2 splicing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Weng, M. W., Hsiao, Y. M., Chiou, H. L., Yang, S. F., Hsieh, Y. S., Cheng, Y. W., Yang, C. H., & Ko, J. L. (2005). Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2. DNA Repair, 4(4), 493-502. https://doi.org/10.1016/j.dnarep.2004.12.006