O-6-METHYLGUANINE-DNA METHYLTRANSFERASE IN TUMORS AND CELLS OF THE OLIGODENDROCYTE LINEAGE

被引：18

作者：

NUTT, CL

COSTELLO, JF

BAMBRICK, LL

YAROSH, DB

SWINNEN, LJ

CHAMBERS, AF

CAIRNCROSS, JG

机构：

[1] LONDON REG CANC CTR,LONDON,ON N6A 4L6,CANADA

[2] UNIV WESTERN ONTARIO,DEPT ONCOL,LONDON,ON N6A 4L6,CANADA

[3] UNIV WESTERN ONTARIO,DEPT PATHOL,LONDON,ON N6A 4L6,CANADA

[4] UNIV WESTERN ONTARIO,DEPT CLIN NEUROL SCI,LONDON,ON N6A 4L6,CANADA

[5] LOYOLA UNIV,MED CTR,NEUROSCI PROGRAM,MAYWOOD,IL 60153

[6] LOYOLA UNIV,MED CTR,DEPT MED,MAYWOOD,IL

[7] APPL GENET INC,FREEPORT,NY

来源：

CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES | 1995年 / 22卷 / 02期

关键词：

D O I：

10.1017/S0317167100040178

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Oligodendrogliomas respond to nitrosourea-based chemotherapy and are induced in rats following transplacental exposure to ethylnitrosourea, observations suggesting that neoplastic and normal cells of the oligodendrocyte lineage are ''sensitive'' to nitrosoureas. Nitrosoureas alkylate DNA at O-6-guanine with repair mediated by O-6-methylguanine-DNA methyltransferase (MGMT). The cytotoxic and carcinogenic properties of the nitrosoureas appear related to MGMT activity. Methods: To explore why oligodendrogliomas respond to chemotherapy, we measured MGMT activity in five chemosensitive human oligodendrogliomas and in rat oligodendrocyte lineage cells. We also measured MGMT activity in rat astrocytes and compared the cytotoxic effects of carmustine (BCNU) on oligodendrocyte lineage cells and astrocytes. Results: Low levels of MGMT activity were found in five of five human oligodendrogliomas. Cultures of neonatal rat glia enriched for oligodendrocyte lineage cells also had low levels of MGMT activity, approximately one-third that found in astrocytes (p < 0.02), and oligodendrocyte lineage cells were more sensitive to BCNU than astrocytes. Conclusions: Low MGMT activity may contribute to the chemosensitivity of some human oligodendrogliomas and rat oligodendrocyte lineage cells also have low levels. If drug resistance mechanisms in tumors reflect the biochemical properties of their cells of origin, then normal glia may serve as a laboratory substitute for human glioma.

引用

页码：111 / 115

页数：5

共 26 条

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