Chromium Toxicity: Reductive Enzymes in Humans.
Final rept. 1 Apr 95-31 Mar 98
MEDICAL COLL OF WISCONSIN MILWAUKEE
Pagination or Media Count:
Several humans displayed marked similarity in the rates and properties of chromium reduction catalyzed by hepatic microsomal enzymes. Kinetic parameters demonstrated significant rates of chromium reduction using chromiumVI concentrations anticipated for occupational exposure, and the reactive intermediate chromiumV was formed. Room air inhibited only a minority of total chromiumVI reduction. Iron, at concentrations well below that of chromiumVI, markedly stimulated the rates and Vmax of chromiumVI reduction in both liver and lung, but did not significantly change other parameters. The iron effect was not altered by O2. Individuals who are simultaneously exposed to chromium and iron, or other compounds that mediate iron release from ferritin, are likely at greater risk for chromium toxicity. Cytochromes P450 and flavin-containing monooxygenase FMO3 were not capable of mediating chromiumVI or ironIII reduction. P450 reductase was a poor mediator of reduction on its own, but played a significant participatory role in chromiumVI reduction. Cytochrome b5 significantly stimulated rates of chromiumVI reduction, probably by acting in cooperation with P450 reductase and b5 reductase. All findings showed significant differences from existing rodent models, emphasizing the need to utilize human studies to understand chromium toxicity in humans.