Abstract
The NADPH-dependent reduction of chromium (VI), a known carcinogen, by human hepatic microsomes was significantly stimulated by 1,4-naphthoquinone (NQ) or 2-methyl-1,4-naphthoquinone (MNQ) under anaerobic conditions. The most pronounced stimulation occurred when quinone concentrations were increased from 1 to 5 muM. Additional, but smaller, increases were seen with subsequent increases in quinone concentration above 5 muM. These quinones also caused pronounced stimulation of chrom ium(VI) reduction by human lung microsomes. Azo and nitroaromatic compounds, as well as methylviologen (Paraquat), seemed to have little effect. Since marked stimulation occurred with levels of NQ and MNQ that were well below those of the initial chromium(VI) concentration, the quinones probably are being redox-cycled through their semiquinone radicals, and these radicals probably are reducing chromium(VI). In support of this occurrence, NQ and MNQ caused a marked stimulation of NADPH consumption under aerobic conditions, with the resulting generation of superoxide. NQ and MNQ alsostimulated chromium(VI) reduction to different extents under room air, depending on the relative ratios of chromium(VI) to oxygen (O2). This suggests that O2 is able to compete with chromium(VI) for the oxidation of the semiquinones. Sincechromium(VI) reduction is associated with the formation of reactive chromium intermediates, individuals who are exposed simultaneously tochromium(VI) and tocertain quinones therefore could be at potentially greater risk for chromium toxicity and carcinogenicity.