Role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by aziridinylbenzoquinones RH1 and MeDZQ.

We aimed to characterize the role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by antitumour quinones RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) and MeDZQ (2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone). Digitonin-permeabilized FLK cells catalyzed NADPH-dependent single- and two-electron reduction of RH1 and MeDZQ. At equitoxic concentrations, RH1 and MeDZQ induced apoptosis more efficiently than the nonalkylating duroquinone or H(2)O(2). The antioxidant N,N'-diphenyl-p-phenylene diamine, desferrioxamine, and the inhibitor of NQO1 dicumarol, protected against apoptosis induction by all compounds investigated, but to a different extent. The results of multiparameter regression analysis indicate that RH1 and MeDZQ most likely induce apoptosis via NQO1-linked formation of alkylating species but not via NQO1-linked redox cycling.

Effect of low copper exposure on the antioxidant system and some immune parameters.

Low-level copper excess was produced in male BALB/c mice by oral supplementation of copper sulfate solution during a 19-w period. The control Group was supplied with pure drinking water and the 2 experimental Groups with CuSO4.5H2O solutions at 120 mg Cu/L or 300 mg Cu/L, respectively. Compared to the control Group, the copper-dosed animals were slightly smaller, the weight of liver was significantly reduced and liver copper content increased. Chronic copper impaired the liver antioxidant defense system by decreasing activities of Cu,Zn-superoxide dismutase and catalase to 14% and 11% respectively. No significant changes were observed in hematological parameters, but flow cytometry revealed altered phenotypic properties of lymphocytes: decreased suppressor (CD8+CD4-), natural killer and its precursor (CD4+CD8+) cell percent, but increased immunoregulatory index (helper (CD4+CD8-)/suppressor (CD8+CD4-) ratio). Prolonged exposure to low copper concentration had been shown a deleterious effect on both antioxidant defense system enzymes and phenotypic properties of immunocompetent cells of mice.