Radiation-Induced Alterations in Serum and Splenic Lysosomal Hydrolases of Rat

Abstract

Abstract : Exposure to ionizing radiation may result in periods of severe stress, nausea and debilitation. The onset of these symptoms as well as other manifestations of radiation sickness could be related to the release of certain proteolytic enzymes, called cathepsins, from lysosomes. In order to examine the possibility that lysosomal proteases might be an etiological factor in the acute radiation syndrome, the levels of cathepsins B1 and D were measured in the serum and spleen homogenates of rats for a period of 22 days following exposure to 1000 rads gamma radiation from Cobalt 60. In addition, beta-glucuronidase, an enzyme frequently employed to measure lysosomal enzyme release, was determined. The median level of serum beta-glucuronidase was elevated only on day 4; significant decreases occurred on days 1, 2 and 9 through 22. Dramatic elevations in serum cathepsin B1 were observed through most of the investigation. The median cathepsin B1 value in serum was significantly elevated on days 3-6 and 9-15. Splenic beta-glucuronidase is increased on day 1, and greatly elevated on days 3-7, after which it declines toward normal values. Splenic cathepsin D rapidly decreased and remained depressed. A biphasic increase in splenic cathepsin B1 on days 1-4 and 10-22 was also observed. The results of this investigation are consistent with the hypothesis that activation and release of lysosomal hydrolases may be an important pathologic event in the later as well as early stages of the acute radiation syndrome. Three possible mechanisms of injury evoked by radiation-induced changes in lysosomal hydrolases are discussed.