title: The use of human epidermal keratinocytes in culture as a model for studying the biochemical mechanisms of sulfur mustard toxicity.
abstract: Human epidermal keratinocytes in culture were studied to evaluate their usefulness in demonstrating toxic events following exposure to sulfur mustard. Exposure of keratinocytes to sulfur mustard over a concentration range of 1-1000 microM HD, reduced NAD + levels from 96% to 32% of control levels. When keratinocytes were exposed to a concentration of 300 microM HD, NAD + levels began to fall at 1 hour and reached a plateau of 47% of control levels at 4 hours. Niacinamide, an inhibitor of the enzyme poly(ADP-ribose) polymerase, partially protected mustard-exposed cells against NAD + depletion. It also protected cellular viability as assessed by vital staining 24 hours after exposure. This protection was not seen in long-term (72 hr) cultures. These studies suggest that human epidermal keratinocytes in culture can serve as a useful in vitro model for research into the biochemical mechanisms of sulfur mustard-induced cutaneous injury.
authors: Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
authors: W J
authors: WJ
authors: Smith
authors: C L
authors: CL
authors: Gross
authors: P
authors: P
authors: Chan
authors: H L
authors: HL
authors: Meier
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008954:Models, Biological; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000032:analysis; D009536:Niacinamide / Q000494:pharmacology
chemical_list: D009243:NAD; D009536:Niacinamide; D009151:Mustard Gas