PROTECTION BY LYSOSOMAL HYDROLASE INHIBITORS AGAINST CYTOTOXICITY OF 2-CHLOROETHYLETHYL SULFIDE

A possible participation of lysosomal hydrolases in the cytotoxicity o f 2-chloroethylethyl sulfide in spleen lymphocytes was investigated us ing inhibitors of lysosomal phospholipases and proteases. Pepstatin (6 mu M) and leupeptin (60 mu M), inhibitors of lysosomal proteases, rai sed the viability of lymphocytes exposed to 2-chloroethylethyl sulfide from 63 to 87 and 88% of control, respectively. Serine protease inhib itors showed no significant effect on viability. Aminoglycoside inhibi tors of lysosomal phospholipases were also found to prevent the decrea se in viability of spleen lymphocytes exposed to 2-chloroethylethyl su lfide, and the effectiveness of these aminoglycosides (30 mu M) was as follows: gentamicin > kanamycin > streptomycin, with viability increa sed to 89, 79 and 67%, respectively. In contrast to a co-operative act ion between leupeptin and gentamicin, the protection by pepstatin was reduced in the presence of gentamicin. Moreover, the order of the amin oglycosides in terms of the extent to which they antagonized the prote ctive action of pepstatin was the same as their order of efficacy in p reventing the cytotoxicity of CEES. It is suggested that inhibitors of lysosomal hydrolases reduce the cytotoxicity of 2-chloroethylethyl su lfide, presumably through lysosomal stabilization in spleen lymphocyte s.