Oxidative stress elevates Ape1/Ref-1 level and increases alkylator resistance

Silber, J.R., Bobola, M.S., Blank, A., Schoeler, K.D., Haroldson, P.D., Huynh, M.B. and Kolstoe, D.D.The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin. Cancer Res. 8: 3008-3018, 2002

Oxidative stress elevates Ape1/Ref-1 and alkylator resistance. Exposure to minimally cytotoxic doses of HOCl (red), an oxidative free radical generator, elevated Ape1/Ref-1 content in SNB19 and concomitantly increased resistance to temozolomide (left panel) and BCNU (not shown). Increased alkylator resistance was accompanied by decreased abasic site content in HOCl-treated cells (right panel). Taken together, these results indicate that increased Ape1/Ref-1-mediated incision at abasic sites contributes to the enhanced alkylating agent resistance of HOCl-treated cells.