CHARACTERIZATION OF SULFUR MUSTARD–INDUCED TOXICITY BY ENZYME HISTOCHEMISTRY IN PORCINE SKIN

Author： Monteiro-Riviere Nancy A. Inman Alfred O.

ISSN： 1537-6524

Source： Toxicology Mechanisms and Methods, Vol.10, Iss.2, 2000-04, pp. : 127-142

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Abstract

The isolated perfused porcine skin flap (IPPSF) has been validated as an invitro model to study the cutaneous toxicology of numerous compounds, including sulfur mustard (bis(2-chloroethyl)sulfide; HD). Enzyme histochemistry of alkaline phosphatase (ALP), acid phosphatase (ACP), and nonspecific esterase (NSE) was performed on skin dosed with HD from the IPPSF. Flaps from the dose response study were treated with 10.0 (n = 5), 5.0 (n = 4), 2.5 (n = 4), 1.25 (n = 3), 0.5 (n = 3), and 0.2 (n = 4) mg/mL HD in absolute ethanol (EtOH) and perfused for 8 h. Flaps from the time response study were treated with 10.0 mg/mL HD in EtOH or the EtOH vehicle and perfused for 1 (n = 4), 3 (n = 4), 5 (n = 4), and 8 h (n = 3). In the time response study, significant differences (SD ) (p < .05) were found in the stratum basale with ALP (3 h HD SD from the 3 h EtOH; 3 h HD SD from the 8 h HD), ACP (3 h HD SD from the 3 h EtOH), and NSE (8 h HD SD from the 8 h EtOH); in the stratum spinosum with NSE (1 h HD SD from the 1 h EtOH; 8 h HD SD from the 8 h EtOH); and in the dermis with NSE (1 h HD SD from the 1 h EtOH). ALP staining was found to be the most sensitive of the enzyme biomarkers in this study, since its intensity increases in response to mild insult and decreases in response to a more severe exposure.