Radiomodification of xanthine oxidoreductase system in the liver of mice by phenylmethylsulfonyl fluoride and dithiothreitol

The widely distributed xanthine oxidoreductase (XOR) system has been shown to be modulated upon exposure of animals to ionizing radiation through the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In t he present work, radiomodification of the XOR system by phenylmethylsulfony l fluoride (PMSF) and dithiothreitol (DTT) was examined using female Swiss albino mice which were irradiated with gamma rays at a dose rate 0.023 Gy s (-1). PMSF, a serine protease inhibitor, and DTT, the sulfhydryl reagent, w ere administered intraperitoneally prior to irradiation. The specific activ ities of XDH and XO as well as the XDH/XO ratio and the total activity (XDH +XO) were determined in the liver of the mice. The inhibition of XO activit y, restoration of XDH activity, and increase in the XDH/XO ratio upon admin istration of PMSF were suggestive of irreversible conversion of XDH into XO mediated through serine proteases, The biochemical events required for the conversion were probably initiated during the early phase of irradiation, as the treatment with PMSF immediately after irradiation did not have a mod ulatory effect. Interestingly, DTT was not effective in modulating radiatio n-induced changes in the XOR system or oxidative damage in the liver of mic e. The DTT treatment resulted in inhibition of the release of lactate dehyd rogenase. However, the protection appears to be unrelated to the formation of TEARS. On the other hand, the presence of PMSF during irradiation inhibi ted radiation-induced oxidative damage and radiation-induced increases in t he specific activity of lactate dehydrogenase. These findings suggest that a major effect of ionizing radiation is irreversible conversion of xanthine to xanthine oxidase. (C) 2000 by Radiation Research Society.