Apurinic/apyrimidinic endonuclease activity is elevated in @entity1 XXXX .

@entity1 @entity1313 @entity5 @entity6471 @entity31482 @entity11
Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to ionizing radiation and alkylating agents in @entity1 cell lines. The major Ap endo in @entity1 cells is @entity6471 , an abundant multi-functional protein also known as @entity6471 , @entity31482 , and Apex. In this work, we assayed Ap endo activity in @entity1 @entity11 to establish correlates with @entity5 characteristics, and in histologically normal brain adjacent to @entity5 to characterize changes in activity accompanying neurocarcinogenesis. To our knowledge, this is the first available analysis of Ap endo activity in @entity1 @entity1313 . Mean activity in 84 @entity11 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 @entity11 was 3.5-fold greater than for low-grade @entity5 (P < or = 4.0 x 10(-5)), a difference observed within all diagnostic types. Activity was correlated with the fraction of S-phase cells in @entity11 (P < or = 0.02), suggesting that proliferation could be a determinant of activity in these @entity5 . Activity was also correlated with S-phase fraction in the majority of @entity11 (P < or = 0.03). Moreover, within the @entity5 , there was a significant relationship between activity and the fraction of aneuploid cells (P < or = 4.0 x 10(-4)). In the 58 cases analyzed, mean activity was 7.3-fold higher in @entity11 than in adjacent histologically normal brain (0.070 +/- 0.10 versus 0.0096 +/- 0.012 fmol/cell/min; P < or = 3.0 x 10(-5)). Increased @entity5 activity was observed in 93% of @entity5 /normal pairs, indicating that elevation of Ap endo activity is characteristic of @entity1 gliomagenesis. The elevation was large within most pairs, being 13-fold on average and > or = 10-fold in 43% of cases. A concomitant increase in @entity6471 protein was observed by Western blotting in the subset of @entity5 /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 @entity11 .
