Study on expression of Glutathione S-transferase M2 gene in human lung cancer and alleviation of DNA damage exposed to benzo [a] pyrene

• Main Authors: Chia-Ying, 黃嘉瑩
• Other Authors: 柯俊良
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/43679068660815575223

碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 95 === Glutathione S transferases(GSTs)are a family of phase II detoxification enzymes that catalyse the conjuation of glutatione(GSH)to a wide variety of endogenous and exogenous electrophilic compounds. In our previous studies, we found that the overexpression of GST M2 gene in H1355 cells prevented BPDE-mediated formation of DNA adducts. Furthermore, by using RT PCR and Real time-PCR, we found that the expression level of GST M2 was lower in lung cancer cells in comparison to normal lung cells. GST Pi expressed both in lung cancer cells and normal lung cells. However, in H1355 cells, GST Pi can not be detected by RT PCR. In comparison with adjacent normal tissue, expression level of GST M2, analyzed by Real Time-PCR, in lung tumor tissue was seven-times lower. However, expression of GST Pi in adjacent normal tissue was two-times higher than that in lung tumor tissue. Poor prognosis is associated with the low expression of GST M2 in lung tumor tissue. Undetectable expression of GST M2 in H1355 was not caused by the deletion of genomic DNA. The reduced expression GST M2 in H1355 cells can not be restored after treatments with histone deacetylase inhibitor: TSA or/and demethylation agent: 5-aza-dC. Neither the methylation of CpG in promoter nor the histone deacetylation contributed to the reduced expression of GST M2 in H1355 cells. The promoter activity of GST M2 was not associated with the polymorphism(C128T)in its promoter by using luciferase reporter assay. Further investigations will be needed to clarify the mechanisms of GST M2 down regulation in lung cancer cells. Comet assay demonstrated that overexpression of GST M2 in H1355 could alleviate B[a]P-mediated DNA damage. Additionally, overexpression of GST M2 in H1355 cells would alleviate B[a]P-mediated S and G2/M phase accumulation. Therefore, these results of this study suggest that lung carcinogenesis and poor prognosis of overall survival were associated with the reduced expression of GST M2 gene.