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.

Cytometric Analysis of DNA Changes Induced by Sulfur Mustard

“…(3,6,7,8) The results of these investigations suggested that resting PBL and actively proliferating HEX demonstrated somewhat different response to HD in both cytotoxicity and depletion of cellular NAD+. Since the dividing basal epidermal cell in skin appears to be the major target of HD, proliferating epithelial cells were used as in vdQ models of HD-induced skin injury to determine the direct effects of HD on call cycle activity.…”

Effects of Mustard Gas on Veterans: A Review

“…Based on the level of exposure and the target organ, symptoms and signs vary differently. In the eye, it has a wide spectrum where it begins with an asymptomatic period following irritation and redness and ends with corneal damage with photophobia, blepharospasm, and temporary blindness (15,25,26).…”

Characterization and Modulation of Proteins Involved in SM Vesication

“…This process may involve changes in intracellular Ca 2+ and calmodulin (CaM; Meier et al, 1984;Gross et al, 1988;Petrali et al, 1990;Smith et al, 1990;Smulson, 1990;Papirmeister et al, 1991;Smith et al, 1991, Rosenthal et al, 1998. Keratinocytes respond to Ca 2+ -signaling pathways in a fashion that makes them unique from other cells, which may explain the exquisite sensitivity of the skin to SM vesication.…”