COMPARISON OF O6-METHYLGUANINE-DNA METHYLTRANSFERASE ACTIVITY IN BRAIN-TUMORS AND ADJACENT NORMAL BRAIN

被引:0
|
作者
SILBER, JR
MUELLER, BA
EWERS, TG
BERGER, MS
机构
[1] UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195
[2] FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,SEATTLE,WA 98104
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中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/10(6) 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/10(6) 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/10(6) 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.
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页码:3416 / 3420
页数:5
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