The role of mitochondria in chromium carcinogenesis

The uptake and reduction of chromium(VI) compounds are crucial to their carcinogenicity. Many cellular systems have been shown to reduce chromium(VI). The ability of mitochondria to reduce chromate in vitro was investigated using rat liver submitochondrial particles (SMPs), which contain the electron transport chain, and isolated rat liver mitochondria. SMPs with NADH as substrate reduced chromate as shown by EPR and UV-VIS spectroscopic studies. Chromate was reduced to a chromium(V) species, which was detectable by EPR. SMPs with succinate as substrate were less effective in reducing chromate relative to NADH-driven chromate-reductase activity. SMPs show a higher rate of oxygen depletion with NADH as substrate as compared to succinate as substrate. In SMPs with NADH as substrate, rotenone, antimycin and cyanide all produced a ∼40% inhibition of chromate-reductase activity. In SMPs with succinate as substrate, cyanide and antimycin produced ∼50% inhibition of chromate-reductase activity and rotenone caused no detectable inhibition. In vivo studies of rats injected with sodium dichromate spiked with 51Cr showed that after 24 hr, chromium was bound preferentially to mitochondrial DNA relative to nuclear DNA by a factor of ∼1500