Effects of Ape1 overexpression on cellular resistance to DNA-damaging and anticancer agents.

摘要: In vitro biochemical studies indicate that Ape1 is the major mammalian enzyme responsible for repairing abasic lesions in DNA and a significant factor processing of specific 3′-replication-blocking termini. Toward addressing role cellular resistance to DNA-damaging anticancer agents, we constructed chinese hamster ovary (CHO) cell line, AA8-Ape1, exhibits 7-fold higher Ape1-dependent nuclease activity; this overexpression abolished upon exposure tetracycline (Tc). comparison AA8 parental control, our data indicates activity not rate-limiting repair cytotoxic damages induced by alkylating agent methyl methanesulfonate (MMS), oxidizing hydrogen peroxide (H2O2), or ionizing radiation (IR). AA8-Ape1 cells did exhibit increased bleomycin following chronic 3-day exposure, but more acute challenges 1 h. Most notably, line displayed ∼1.7-fold elevated replication-blocking nucleoside analog dioxolane cytidine (L-OddC); improved was abrogated addition Tc medium. These demonstrate MMS- H2O2-induced damage, may dictate sensitivity bleomycin, depending on dosing scheme, first time, can influence anticancer/antiviral antimetabolite L-OddC.