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Sulfur Mustard-Induced Apoptosis in Hairless Guinea Pig Skin
Robert K. Kan
Comparative Pathology Branch, Comparative Medicine Division, Robert.Kan{at}apg.amedd.army.mil
Christina M. Pleva
Comparative Pathology Branch, Comparative Medicine Division
Tracey A. Hamilton
Comparative Pathology Branch, Comparative Medicine Division
Dana R. Anderson
Pharmacology, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400
John P. Petrali
Comparative Pathology Branch, Comparative Medicine Division
The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC) were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.
Key Words: Sulfur mustard • apoptosis • hairless guinea pigs • skin • basal cells • microvesicles.
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Toxicologic Pathology, Vol. 31, No. 2,
185-190 (2003)
DOI: 10.1080/01926230390183661
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