Iron stimulates the rate of reduction of hexavalent chromium by human microsomes

The NADPH-dependent reduction of chromium (VI), a known carcinogen, byhepatic microsomes was very similar for all five humans examined, with anapparent Km for chromate of 1.04-1.68 microM, and a Vmax of 10.4- 10.7nmol/min/mg protein. Inhibitor studies indicate no role for cytochromeP450s, but a prominent role for flavoproteins, which could include P450reductase, flavin-containing mono-oxygenase and cytochrome b5. Relative toanaerobic conditions, Cr(VI) reduction was inhibited only 26-37% by roomair, which indicates that human microsomal Cr(VI) reduction could stillproceed at significant rates, even in tissues with high O2 tensions.Studies with lung microsomes from one human exhibited Vmax and Km valuesthat were two-thirds lower and 2.8-fold greater, respectively, than thoseof hepatic microsomes from the same individual; other Cr(VI)-reducingparameters were similar for lung and liver. Various forms of exogenousiron, when present at 0.76-6.3 microM, markedly enhanced both liver andlung microsomal rates and Vmax of Cr(VI) reduction, but did notsignificantly alter the other Cr(VI)- reducing parameters (Km, effects ofO2 and inhibitors). These iron levels were 3.1- to 26-fold lower than theinitial Cr(VI) concentration, which suggests that iron is serving acatalytic role. The ratio of human microsomal Cr(VI) reduction rates underaerobic versus anaerobic conditions remained fairly constant, regardless ofiron concentration. Small increases in intracellular iron could thereforelead to large increases in the rate and extent of microsomal Cr(VI)reduction. Individuals that are simultaneously exposed to Cr(VI) and toagents that increase intracellular iron could therefore be at potentiallygreater risk for Cr(VI) toxicity and carcinogenicity.