Mn(III)-desferrioxamine superoxide dismutase-mimic: alternative modes of action. 
Various low-molecular-weight copper chelates have been synthesized to mimic superoxide dismutase (SOD) by catalyzing O2-.  dismutation.  However, in the presence of cellular proteins, such chelates dissociate and thereby lose their SOD-mimetic activity.  In contrast, desferrioxamine-Mn(III) 1:1 chelate (DF-Mn), an SOD-mimic that affords protection from oxidative damage, reportedly is stable in the presence of serum albumin.  DF-Mn, unlike SOD, is reported to permeate the membrane of at least one cell type and can protect cells by detoxifying intracellular O2-.. Recently DF-Mn was shown to protect hypoxic cells from H2O2-induced damage.  Such results suggest that DF-Mn can protect cells from O2-.-independent damage by alternative mechanisms.  This study examines such possibilities.  To avoid O2-.  participation in the damaging process, killing of monolayered V79 Chinese hamster cells was induced in a hypoxic environment by t-butyl hydroperoxide (t-BHP).  Damage induced by t-BHP was inhibitable by DF-Mn.  DF-Mn was also found to rapidly oxidize iron(II)-bound DNA.  Additionally, once DF-Mn oxidizes Fe(II) or Cu(I), the DF moiety of DF-Mn dissociates and rapidly binds to Fe(III) or Cu(II).  Without excluding the possibility that DF-Mn protects cells by facilitating the removal of O2-.,  the present results show that this SOD-mimic can confer protection from cytotoxic processes independent of O2-.  or of O2-.-derived active species.