The current objective is to characterize free radical reactions in cellular injury caused by mineral particles. Our major findings have been the following: (1) Freshly fractured quartz particles generated hydrogen peroxide, superoxide radical, hydroxyl radical and singlet oxygen upon reaction with aqueous medium. The mechanism of their generation involves metal ion-mediated reactions and requires molecular oxygen. These reactive oxygen species caused DNA double-strand breaks, dG hydroxylation, and lipid peroxidation. (2) Tetrandrine was found to be an antioxidant. Its reaction rate with hydroxyl radical is 1.4 x 10E10/M/sec. Tetrandrine caused inhibition on quartz-induced lipid peroxidation. This antioxidant properties may provide a basis for the prevention and treatment of silicosis. (3)(a) Peroxynitrite decomposition generates unidentified oxidizing intermediate and not free hydroxyl radical; in the presence of superoxide dismutase, peroxynitrite generates a very reactive and oxidative nitronium ion. (b) Peroxynitrite reacts with thiols and ascorbate to generate thiyl and ascorbate radicals. (4) Chromium(VI) and vanadium(V) were found to be readily reduced by thiols and ascorbate to generate Cr(V) and V(IV), which generate hydroxyl radicals via a Fenton type reaction. Cellular chelators (anserine, GSH and cysteine) can modulate the oxidation potentials of Cobalt(II) and Nickel(II) and make them efficiently generate oxygen free radicals not only from hydrogen peroxide, but also from lipid hydroperoxides. The oxygen free radicals generated by these reactions cause DNA double-strand break and dG hydroxylation. (5) Direct low frequency electron spin resonance (ESR) measurements provide evidence that Cr(V) is generated from Cr(VI) in whole living animals. Using 5,5- dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap, an ESR signal was observed, indicating the DMPO adduct of sulfur trioxide anion radical. These results open a new avenue for studying metal-ion metabolism and free radical reaction in whole living animals.
