Ascorbate (
vitamin C) is a
biological reductant of the human
carcinogen chromium(VI). The product of this reaction is presumed to be dehydroascorbate. However, we have found that
chromium(VI) can also react with dehydroascorbate. This reaction was monitored by UV/ visible and electron paramagnetic resonance (EPR) spectroscopies. In
sodium acetate buffer at pH 3.8, the reaction of
chromium(VI) and excess dehydroascorbate produced
chromium(V) and
chromium(IV) intermediates. At high reaction concentration, the
chromium(V) intermediate formed an EPR silent dimer, which dissociated upon dilution to lower concentration. UV/ visible experiments at pH 3.8 demonstrated that
manganese(II) catalyzed the disproportionation of
chromium(IV) to
chromium(V) and
chromium(III). The ability of the reaction intermediates to induce strand breaks in pBR322
DNA was determined at pH 3.8 and pH 5.8. At pH 3.8,
chromium(IV) appeared to be the major species responsible for induction of strand breaks because the time course for formation of strand breaks did not parallel that of
chromium(V), and strand breaks were decreased in the presence of the
chromium(IV) scavenger
manganese(II). At pH 5.8, fewer strand breaks were observed; however, the time course for their formation followed that of
chromium(V). There has been much effort devoted to identification of the intermediate responsible for the induction of strand breaks during reactions of
chromium(VI) with
biological reductants. The current results suggest that it is not a single type of species that universally produces the
DNA strand breaks observed in different
chromium(VI) systems and that the reactivity of intermediates will depend on the chosen experimental conditions. Understanding this variability in
chromium(VI) reactions may help to resolve the conflicting results from in vitro studies that are aimed at deciphering mechanisms of
chromium(VI)-induced
cancers.