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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Abbreviations
- HD:
-
sulfur mustard, 2,2′-dichlorodiethyl sulfide
- NAD+:
-
nicotinamide adenine dinucleotide
- ADP:
-
adenosine diphosphate
- HEK:
-
human epidermal keratinocytes
- PI:
-
propidium iodide
References
BOYCE, S.T. and HAM, R.G. (1983). Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J. Invest Dermatol.81:33s-40s.
GROSS, C.L., MEIER, H.L., PAPIRMEISTER, B., BRINKLEY, F.B., and JOHNSON, J.B. (1985). Sulfur mustard lowers nicotinamide adenine dinucleotide concentrations in human skin grafted to athymic nude mice. Toxicol. Appl. Pharmacol.81:85–90.
JACOBSON, E.L. and JACOBSON, M.K. (1976). Pyridine nucleotide levels as a function of growth in normal and transformed 3T3 cells. Arch. Biochem. Biophys.175:627–634.
MC ADAMS, A.J. (1956). A study of mustard vesication. J. Invest. Dermatol.26:317–326.
MEIER, H.L., GROSS, C.L. and PAPIRMEISTER, B. (1987). 2,2′-Dichlorodiethyl sulfide (sulfur mustard) decreases NAD+ levels in human leukocytes. Toxicol. Lett.39:109–122.
PAPIRMEISTER, B., GROSS, C.L., PETRALI, J.P. and HIXSON, C.J. (1984). Pathology produced by sulfur mustard in human skin grafts on athymic nude mice. I. Gross and light microscopic changes. J. Toxicol.-Cut & Ocular Toxicol.3:371–391.
PAPIRMEISTER, B., GROSS, C.L., MEIER, H.L., PETRALI, J.P. and JOHNSON, J.B. (1985). Molecular basis for mustard-induced vesication. Fundament. appl. Toxicol.5:S134-S149.
RENSHAW, B. (1947). Observations on the role of water in the susceptibility of human skin to injury by vesicant vapors. J. Invest. Dermatol.9:75–85.
SCHWARZ, F. (1937). Experimental studies on mustard action. Protar.3:34–37.
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Smith, W.J., Gross, C.L., Chan, P. et al. The use of human epidermal keratinocytes in culture as a model for studying the biochemical mechanisms of sulfur mustard toxicity. Cell Biol Toxicol 6, 285–291 (1990). https://doi.org/10.1007/BF02443803
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DOI: https://doi.org/10.1007/BF02443803