IRON STIMULATES THE RATE OF REDUCTION OF HEXAVALENT CHROMIUM BY HUMANMICROSOMES

The NADPH-dependent reduction of chromium (VI), a known carcinogen, by hepatic microsomes was very similar for all five humans examined, wit h an apparent K-m for chromate of 1.04-1.68 mu M, and a V-max of 10.4- 10.7 nmol/min/mg protein. Inhibitor studies indicate no role for cytoc hrome P450s, but a prominent role for flavoproteins, which could inclu de P450 reductase, flavin-containing mono-oxygenase and cytochrome b(5 ). Relative to anaerobic conditions, Cr(VI) reduction was inhibited on ly 26-37% by room air, which indicates that human microsomal Cr(VI) re duction could still proceed at significant rates, even in tissues with high O-2 tensions. Studies with lung microsomes from one human exhibi ted V-max and K-m values that were two-thirds lower and 2.8-fold great er, respectively, than those of hepatic microsomes from the same indiv idual; other Cr(VI)-reducing parameters were similar for lung and live r. Various forms of exogenous iron, when present at 0.7-6.3 mu M, mark edly enhanced both liver and lung microsomal rates and V-max of Cr(VI) reduction, but did not significantly alter the other Cr(VI)-reducing parameters (K-m, effects of O-2 and inhibitors). These iron levels wer e 3.1- to 26-fold lower than the initial Cr(VI) concentration, which s uggests that iron is serving a catalytic role, The ratio of human micr osomal Cr(VI) reduction rates under aerobic versus anaerobic condition s remained fairly constant, regardless of iron concentration. Small in creases in intracellular iron could therefore lead to large increases in the rate and extent of microsomal Cr(VI) reduction. Individuals tha t are simultaneously exposed to Cr(VI) and to agents that increase int racellular iron could therefore be at potentially greater risk for Cr( VI) toxicity and carcinogenicity.