Evaluation of O6-methylguanine DNA methyltransferase activity in patients with gastric cancer.
O6-Methylguanine DNA methyltransferase (O6-MGMT) reverses DNA alkylation damage produced alkylating agents. O6-MGMT is also a major determinant of cellular resistance to adjuvant chemotherapy with alkylating drugs. O6-MGMT activity was measured in samples from patients with gastric cancer, including tumor, adjacent normal appearing mucosa, and peripheral blood leukocytes (PBL). O6-MGMT activity of PBL from healthy individuals was evaluated as control. There was no significant difference between controls and patients for O6-MGMT activity in PBL. O6-MGMT activity was significantly increased in tumor tissue. Tumor O6-MGMT activity was found to be independent from tumor subgroups and tumor grade. A positive correlation was determined between O6-MGMT activity in tumor and in circulating PBL. The results indicate that O6-MGMT, a defense protein against alkylating agent-mediated carcinogenesis, increased in gastric tumors. This may explain the low response rate to drug combinations, including chloroethylnitrosoureas, exhibited by patients with gastric cancer.
Dinçer
Yildiz
Y
Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, 34300, Turkey. stare63@yahoo.com
Akçay
Tülay
T
Tortum
Osman B
OB
Alademir
Zeynep
Z
Onen
Sinan
S
Doğusoy
Gülen
G
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000097:blood / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000097:blood / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000097:blood / Q000201:enzymology*
D019853:O(6)-Methylguanine-DNA Methyltransferase