GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE AS A BIOCHEMICAL MARKER OF CYTOTOXICITY BY VINYL SULFONES IN CULTURED MURINE SPLEEN LYMPHOCYTES

Recently, vinyl sulfones have been observed to selectively inhibit gly ceraldehyde-3-phosphate dehydrogenase (GAPDH), which is an important A TP-generating enzyme in glycolysis. The possibility of using GAPDH as a biochemical parameter of cytotoxicity by vinyl sulfones was investig ated using mouse lymphocytes. Incubation of lymphocyte GAPDH with ethy lvinyl sulfone resulted in a pseudo-first-order loss of enzyme activit y. The exposure of lymphocytes to ethylvinyl sulfone resulted in the d ecrease of GAPDH activity followed by ATP depletion and cell death, wh ich were both dependent on the concentration of ethylvinyl sulfone. A further study on the time-dependent change indicated that cell death w as preceded by ATP loss. Compared to ethylvinyl sulfone, divinyl sulfo ne was more than 8 times more potent in causing either ATP depletion o r cell death.