The use of human epidermal keratinocytes in culture as a model for studying the biochemical mechanisms of sulfur mustard toxicity |
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Authors: | William J Smith PhD Clark L Gross MS Philip Chan MD Henry L Meier PhD |
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Institution: | (1) Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland;(2) USAMRICD, Attn: SGRD-UV-PB, 21010-5425 Aberdeen Proving Ground, MD |
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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 μM HD, reduced
NAD+ levels from 96% to 32% of control levels. When keratinocytes were exposed to a concentration of 300 μM 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 usefulin vitro model for research into the biochemical mechanisms of sulfur mustard-induced cutaneous injury. |
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Keywords: | sulfur mustard keratinocytes vesication in vitro models |
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