CHROMATE-INDUCED CHROMIUM(V) FORMATION IN LIVE MICE AND ITS CONTROL BY CELLULAR ANTIOXIDANTS - AN L-BAND ELECTRON-PARAMAGNETIC-RESONANCE STUDY

A recent note from our laboratory reported that L-band (1.2 GHz) elect ron paramagnetic resonance spectroscopy can be utilized in detecting t he formation of Cr(V) intermediates from chromate-treated whole mice. Since Cr(V) is thought to be one of the key species in the mechanism o f chromate's toxicity, we carried out additional measurements with imp roved sensitivity. The new spectra show partially resolved hyperfine s tructure from protons that suggests that the Cr(V) ion is ligated to N AD(P)H moieties via oxygens. Using laboratory-synthesized Cr(V) (K3CrO 8) as a standard, the yield of Cr(V) formation was estimated to be 153 +/- 12 nmol after intravenous injection of 100 mu l of 100 mM sodium dichromate into mice. Pretreatment of the mice with ascorbic acid and glutathione significantly reduced the Cr(V) formation yield in a dose- related manner, while pretreatment with NADH had the opposite effect. Injection of ascorbic acid also had the effect of enhancing the rate o f Cr(V) disappearance in vivo. By comparing these results with in vitr o results utilizing L-band as well as X-band (9.6 GHz) measurements, w e conclude that L-band spectroscopy can indeed be effectively utilized for following the metabolism of Cr(V) in live mice and that Cr(V) for mation can be controlled by utilizing cellular antioxidants in vivo. ( C) 1995 Academic Press, Inc