Inhibition of Glutathione Synthesis
نویسندگان
چکیده
A preliminary account of this work was presented at the 66th Annual Meeting of the Federation of American Societies for Experimental Biology, April 1982. Dr. Nathan is an Irma T. Hirschl Career Scientist. Address reprint requests to Dr. Arrick. Received for publication 23 June 1982 and in revised form 18 October 1982. with BSO alone results in near-complete GSH depletion without loss of cell viability, SL-mediated cytolysis is probably not a result of GSH depletion. We have demonstrated, however, a critical role for GSH synthetic capacity as a determinant of tumor cell susceptibility to cytolysis by SL. GSH also plays an important role in cellular defense against oxidative injury. Vernolepin, acting as a GSH-depleting agent, markedly sensitized tumor cells to lysis by H202 (>6.5-fold increase with 20 gg/ml of vernolepin). These findings suggest the possibility that the coordinated deployment of sulfhydryl-reactive antitumor agents, BSO, and oxidative injury might constitute an effective chemotherapeutic strategy.
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