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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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

Fingerprint

Benzo(a)pyrene
Glutathione Transferase
DNA Damage
Carcinoma
Lung
DNA
Detoxification
Cells
Cell Line
Polymerase Chain Reaction
Phase II Metabolic Detoxication
Environmental Carcinogens
Human Activities
Carcinogens
Catalyst activity
Complementary DNA
Clone Cells
Enzyme-Linked Immunosorbent Assay

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., ... 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

Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2. / Weng, Mao W.; Hsiao, Yi M.; Chiou, Hui Ling; Yang, Shun F.; Hsieh, Yih Shou; Cheng, Ya W.; Yang, Chieh Hsiang; Ko, Jiunn Liang.

In: DNA Repair, Vol. 4, No. 4, 04.04.2005, p. 493-502.

Research output: Contribution to journalArticle

Weng, MW, Hsiao, YM, Chiou, HL, Yang, SF, Hsieh, YS, Cheng, YW, Yang, CH & Ko, JL 2005, 'Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2', DNA Repair, vol. 4, no. 4, pp. 493-502. https://doi.org/10.1016/j.dnarep.2004.12.006
Weng, Mao W. ; Hsiao, Yi M. ; Chiou, Hui Ling ; Yang, Shun F. ; Hsieh, Yih Shou ; Cheng, Ya W. ; Yang, Chieh Hsiang ; Ko, Jiunn Liang. / Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by glutathione S-transferase M2. In: DNA Repair. 2005 ; Vol. 4, No. 4. pp. 493-502.
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