Studies on the modification of the cellular response to injury

Extracellular acidosis (pH 6.5) was found to significantly retard the response of Ehrlich ascites tumor cells (EATC) to direct plasma membrane injury with the non-penetrating organic mercurial compound, p-chloromercuribenzene sulfonic acid (PCMBS). Treatment of cells with 1 mM PCMBS resulted in loss of viability of all cells by 45 minutes at pH 7.4, and by 90 minutes at pH 6.5. Pregression of cellular changes through the various stages of cell injury at the ultrastructural level was correspondingly slower at pH 6.5. The results support the concept that stage 3 of cell injury, associated with condensed mitochondria, dilated ER and swollen cell sap is compatible with cell survival, while stage 5 with high amplitude swelling of mitochondria, fragmentation of membrane systems, and beginning of karyolysis is characteristic of irreversible injury. All cells entered stage 3 at 7.5 minutes at pH 7.4, while essentially all cells entered stage 5 by 45 minutes. At pH 6.5, stage 3 was maintained for 45 minutes and 100% of the cells entered stage 5 by 90 minutes. Although the mechanism of the protection against PCMBS-induced injury is not known, the present electron microscopical results are compatible with the hypothesis that the extracellular acidosis acts to partially stabilize plasma membrane, perhaps by interaction with sulfhydryl (SH) groups.