Expression of glutathione S-transferase M2 in stage I/II non-small cell lung cancer and alleviation of DNA damage exposure to benzo[a]pyrene.
Glutathione S-transferases (GSTs) are a family of inducible enzymes that are important in carcinogen detoxification. GST-Mu class is showing the high activity towards most polycyclic aromatic hydrocarbon (PAH) epoxide. Our objective is to clarify the expression of GST-M2 in non-small-cell lung carcinoma (NSCLC) patients and to determine the role of GST-M2 in protecting against DNA damage. We detected changes in GST-M2 expression at mRNA levels with a panel of lung cell lines and clinical samples of malignant and paired adjacent non-malignant tissues from 50 patients with stage I or II non-small-cell lung carcinoma using real-time RT-PCR. Comet assay and gamma-H2AX were used to clarify whether DNA damaged was protected by GST-M2. Our data demonstrate that the expression of GST-M2 in tumor tissues is significantly lower than in paired adjacent non-malignant tissues (p=0.016). Loss of GST-M2 is closely associated with age, gender, T value, N value and cell differentiation (p<0.05) in early stage I/II patients. Downregulation of GST-M2 is mediated through aberrant hypermethylation in lung cancer cell lines. Protection against B[a]P-induced DNA damage by GST-M2 in lung cancer cells was detected by Comet assay and gamma-H2AX. In conclusion, DNA hypermethylation altered and reduced GST-M2 expression that resulted in susceptible to benzo[a]pyrene (B[a]P) induced DNA damage. It implies that GST-M2 reduction occurs prior to tumorigenesis.
Tang
Sheau-Chung
SC
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Sheu
Gwo-Tarng
GT
Wong
Ruey-Hong
RH
Huang
Chia-Ying
CY
Weng
Mao-Wen
MW
Lee
Li-Wen
LW
Hsu
Chung-Ping
CP
Ko
Jiunn-Liang
JL
D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D012334:RNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012334:RNA, Neoplasm; D001564:Benzo(a)pyrene; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2