REDUCTION OF CHROMIUM(VI) TO CHROMIUM(V) BY HUMAN MICROSOMAL ENZYMES: EFFECTS OF IRON AND QUINONES

The NADPH- and NADH-dependent reduction of chromium(VI), a known carcinogen, by human hepatic and lung microsomes likely proceeds through cytochrome b 5 as the common mediator of electron transfer to Cr(VI). Consistent with the ability of cytochrome b 5 to transfer one electron at a time, Cr(V) was generated as a transient intermediate during human microsomal Cr(VI) reduction. The redox cycling of small amounts of iron or quinones significantly accelerated the rate of Cr(VI) reduction, which should accelerate Cr(V) formation. However, Cr(V) did not accumulate under these conditions, suggesting that Fe(II) and semiquinones also reduce Cr(V). This could accelerate the formation of Cr(IV), a highly reactive intermediate. An indirect electron paramagnetic resonance (EPR) method suggested that Cr(IV) was produced during microsomal Cr(VI) reduction. Since iron and quinones significantly altered the rates of formation of reactive Cr intermediates, they could potentially influence cytotoxic damage associated with these intermediates.