PRESENCE OF METHENAMINE GLUTATHIONE MIXTURES REDUCES THE CYTOTOXIC EFFECT OF SULFUR MUSTARD ON CULTURED SVK-14 HUMAN KERATINOCYTES IN-VITRO/

1 The basal epidermal keratinocytes of the skin are a main target for the vesicating agent, sulphur mustard (SM). A human keratinocyte cell line (SVK-14) has been used to model the effects of SM on the basal ep idermal keratinocytes and subsequently to test the efficacy of potenti al prophylactic compounds in reducing the SM-induced cytotoxicity. 2 T he cultures were pretreated with mixtures of methenamine (HMT) and glu tathione (GSH) for 1 h prior to exposure to 10 mu M SM. The viability of the cultures was then assessed using neutral red (NR) dye uptake an d crystal violet DNA staining assays at 24 h intervals post exposure. 3 Pretreatment led to a 1.9 fold increase in culture viability (NR ass ay) compared to those exposed to SM only, and a 2.3 fold increase in c ell number (crystal violet assay). Photomicrography showed that pretre atment preserved the morphology of the cultured cells and maintained t heir mitotic activity whereas those exposed to SM only show non-prolit erative cultures with extensive cellular damage. 4 The results of this study show that it is possible to protect mitotically active cultures from the effects of SM, however the measures must be in place prior t o SM exposure.