Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas.
Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas.
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发表时间：
2001-11
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通讯作者：
M. Bobola;A. Blank;M. Berger;B. A. Stevens;J. Silber
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作者：
M. Bobola;A. Blank;M. Berger;B. A. Stevens;J. Silber
Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to ionizing radiation and alkylating agents in human cell lines. The major Ap endo in human cells is Ape1, an abundant multi-functional protein also known as Ref-1, Hap-1, and Apex. In this work, we assayed Ap endo activity in human adult gliomas to establish correlates with tumor characteristics, and in histologically normal brain adjacent to tumors to characterize changes in activity accompanying neurocarcinogenesis. To our knowledge, this is the first available analysis of Ap endo activity in human brain tumors. Mean activity in 84 gliomas of different diagnostic types and grades was 0.072 +/- 0.095 fmol abasic sites incised/cell/min, ranging approximately 550-fold from 0.00077 to 0.42. The mean for high-grade gliomas was 3.5-fold greater than for low-grade tumors (P or = 10-fold in 43% of cases. A concomitant increase in Ape1 protein was observed by Western blotting in the subset of tumor/normal pairs examined. A clinically important consequence of the increase in Ap endo activity that accompanies neurocarcinogenesis may be enhanced resistance to the radiotherapy and alkylating agent-based chemotherapy that are mainstays of adjuvant therapy for malignant gliomas.
