Methylguanine DNA Methyl Transferase Activities, Glutathione S Transferase and Nitric Oxide in Bladder Cancer Patients

Abstract

Tumor formation is a multistep process that can be divided in to the stages of tumor initiation, promotion, and progression. DNA repair protein; MGMT is a key suicide enzyme that repairs the mispairing base methylguanine, which is induced in DNA as a minor lesion. The glutathione S transferases (GSTs) are a family of enzymes that are important to protect against alkylating agents. Nitric oxide, contributes to the regulation of tumor angiogenesis. A substantial body of experimental evidence supports the hypothesis that tumor angiogenesis is fundamental for the growth and metastasis of solid tumors. We measured the activities of GST, MGMT, and levels of NO₃⁻/NO₂⁻ in the leukocytes from patients with bladder carcinoma and healthy controls and activities of MGMT in the tissue from patients with bladder carcinoma and adjacent normal tissue in bladder. Both GST and tissue MGMT activites were significantly increased in the patient group. There was no significant difference between controls and patients for MGMT activity in peripheral blood leukocytes (PBL). Nitrate/nitrite levels in PBL, there was no significant difference between controls and patients. Nitrate/nitrite levels were increased in G2-G3 tumors. In conclusion, we determined high concentrations of nitrite in leukocytes are suspected alkylation damage by induction nitrosamine. Increased DNA alkylation damage may lead the stimulation of MGMT and GST.

Keywords:

• Bladder cancer
• GST
• MGMT
• Nitric oxide