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Departments of Neurological Surgery [J. R. S., T. G. E., M. S. B.] and Epidemiology [B. A. M.], University of Washington, Seattle, Washington 98195, and Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [B. A. M.]
We assayed the activity of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in 60 human brain tumors to assess the effects of tumorigenesis in brain on DNA repair capability. Activity was not detectable (<0.5 fmol/106 cells, i.e., <300 molecules/cells) in 27% of the tumors. Measurable MGMT varied by more than 2 orders of magnitude, 0.5–104.1 fmol/106 cells. Mean tumor MGMT levels did not differ between the sexes but did vary widely between diagnostic groups. A significant inverse correlation was observed between tumor MGMT activity and patient age. We also assayed MGMT activity in overlying, histologically tumor-free brain resected with 25 tumors. Of these samples, 52% had no detectable MGMT activity, and the remainder had activity comparable to that in tumors ranging from 0.7–21.8 fmol/106 cells. MGMT activity in normal brain was also inversely correlated with patient age. For 15 of 25 (60%) paired samples, tumor activity was 2 to >38-fold greater than that of normal brain; for 4 pairs (16%) tumor activity was 2.5 to >17-fold lower than that of normal brain; the remaining 6 (24%) had no detectable activity in both tumor and normal tissue. These differences in the magnitudes and distributions of activities for tumor versus normal brain tissue were significant (P = 0.02), demonstrating that tumorigenesis in brain is often accompanied by marked elevation of MGMT.
1 This work was supported by NIH grants K08 NS01253-01 (M. S. B.), T32NS07144-13, and 1-R01-CA47082 (B. A. M.).
2 To whom reprint requests should be addressed, at the Department of Neurological Surgery, RI-20, University of Washington, Seattle, WA 98195.
Received 2/ 9/93. Accepted 5/11/93.
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