INJURY-SPECIFIC CYTOTOXIC RESPONSE OF TUMOR-CELLS AND ENDOTHELIAL-CELLS

Cytotoxicity indicated by increased release of prelabeled (51)chromium (Cr-51) and lactate dehydrogenase (LDH) was studied in human prostate cancer and melanoma cells in cell culture following irradiation or ex posure to several injurious substances. These changes were compared to those observed in bovine aortic endothelial cells (BAEC) subjected to identical treatments. Further, the effect of irradiation on plasminog en activator (PA) secretion from prostate cancer cells, and the effect of glycine on radiation-induced cytotoxicity in BAEC were also invest igated. Radiation, lipopolysaccharide and xanthine/xanthine oxidase st imulated no release of Cr-51 gy LDH from tumor cells, while these trea tments induced a dose- and time-related loss of those cytotoxic indica tors from BAEC. Protease, elastase and Triton X-100 incited loss of Cr -51 and LDH from all three cell types. Radiation, lipopolysaccharide a nd xanthine/xanthine oxidase have been shown to cause cell injury via a common pathogenic pathway of oxidant generation. Tumor cells appear quite resistant to oxidant stress. Cell damage precipitated by proteas e, elastase and Triton probably involves hydrolysis of proteins and ph ospholipids in the cell membrane, leading to an increased leakage of i ntracellular proteins such as LDH and those bound with Cr-51. Radiatio n caused a dose- and time-related reduction in the secretion of PA fro m prostate cancer cells. PA is alleged to play a role in tumor metasta sis; the reduced secretion could be another beneficial effect of radia tion, in addition to interruption of cell proliferation, in the impedi ment of tumor growth and spread. Glycine diminished cytotoxic injury o f BAEC inflicted by radiation. This amino acid may prove useful in off ering a degree of protection of normal tissue against radiation associ ated side-effects.