SULFUR MUSTARD-INDUCED BIOCHEMICAL-ALTERATIONS IN PROLIFERATING HUMAN-CELLS IN CULTURE

Human epidermal keratinocytes (HEK), human epithelial tumor cells (HeLa), and actively proliferating human peripheral blood lymphocytes (PBL) were used as in vitro model systems to investigate the biochemical sequelae of sulfur mustard-induced injury. Sulfur mustard exposure of all three proliferating cell types resulted in inhibition of cell cycle progression in the early S phase. Cytotoxicity due to sulfur mustard was higher in proliferating, mitogen-stimulated PBL than in resting PBL. Niacinamide, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase, partially prevented the loss of cellular NAD+ in sulfur mustard-treated cells. Niacinamide also protected against the cytotoxic effects of sulfur mustard for 24 hr. However, this protection waned when cell growth was allowed to proceed up to 72 hr.