Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes.

UNLABELLEDThe anticancer activity of aziridinyl-quinones is mainly attributed to theirNAD(P)Hquinone oxidoreductase 1 (NQO1)-catalyzed two-electron reduction into DNA-alkylating products. However, little is known about their cytotoxicity in primary cells, which may be important in understanding their side effects. We found that the cytotoxicity of aziridinyl-unsubstituted quinones (n = 12) in mice splenocytes with a low amount of NQO1, 4 nmol × mg(-1) × min(-1), was caused mainly by the oxidative stress. Aziridinyl-benzoquinones (n = 6) including a novel anticancer agent RH1 were more cytotoxic than aziridinyl-unsubstituted ones with the similar redox properties, and their cytotoxicity was not decreased by an inhibitor of NQO1, dicumarol. The possible reasons for their enhanced cytotoxicity are discussed.