HISTOPATHOLOGIC FEATURES SEEN WITH DIFFERENT ANIMAL-MODELS FOLLOWING CUTANEOUS SULFUR MUSTARD EXPOSURE

In an effort to understand the pathophysiology of sulfur mustard (2,2' dichlorodiethyl sulfide, HD)-induced cutaneous lesions, a number of a nimal models have been used. Animal models have been and will continue to be used in the development of therapeutic strategies to protect ag ainst and/or moderate lesions, and to potentiate wound healing after H D exposure. Upon reviewing the histopathologic features seen after I-I D-exposure, we propose roles for different animal models in I-ID-resea rch. Hematoxylin and eosin slides from protocols done originally as do se response studies for either liquid or vapor HD-exposures were exami ned. The animal models reported include the hairless guinea pig (HGP), weanling pig (WP), mouse ear (ME) and hairless mouse (HM). In all the se animal models, HD induces subepidermal blister formation as well as epidermal cell death. The HGP appears to be the most sensitive model for epidermal necrosis. The HGP and, to a lesser degree, the HM react with a marked neutrophilic infiltrate. The ME provides a quantitative measure for HD effects and a mild inflammatory infiltrate similar to w hat is seen in human skin. Doses necessary to produce microblister for mation in the WP are usually associated with more significant stromal and vascular changes than in other animal models. In addition to a qua ntitative measure of the HD effect and a mild inflammatory response, t he cost, as well as the availability of specific antibodies, and DNA a nd RNA probes and primers gives the ME advantages for both drug screen ing and for the study of the pathophysiology of HD-induced cutaneous l esions. The sensitivity of the HGP and the abundant experience with va por exposures establishes a place for this animal model in barrier cre am and drug screening. The similarity of WP skin to human skin is impo rtant in the study of wound healing after HD exposure, as well as in t he study of the pathophysiology of the cutaneous lesion and in more de finitive therapeutic studies.