PATHOGENESIS OF 2,2'-DICHLORODIETHYL SULFIDE IN HAIRLESS GUINEA-PIGS

Developing skin lesions on hairless guinea pigs due to 2,2'-dichlorodi ethyl sulfide (sulfur mustard, HD) exposure were examined to determine the time course for the appearance of histopathologic markers in rela tionship to skin NAD+ and NADP(+) content after HD exposure. Hairless guinea pig skin was exposed to HD for 8 min by means of a vapor cup. S kin punches were taken at 1, 2, 4, 8, 12, 16, 20 and 24 h after HD exp osure. Intracellular edema (IE) appeared at 2 h and increased steadily over 24 h. Epidermal necrosis (EN) and pustular epidermatitis (PE) de veloped at 8 h and reached a maximum at 16 h. Follicular necrosis (FN) appeared at 8 h and increased up to 24 h. Microvesicles (MV) develope d between 12-16 h reaching a maximum at 24 h. Niacinamide (750 mg/kg, ip) pretreatment (30-min) reduced the incidence of MV (40%) and FN (45 %) at 24 h, but did not reduce IE, EN, or PE. In all animals, skin NAD (+) content decreased to a minimum (20% of control) at 16 h, but NAD() decreases did not precede microvesicle formation. Skin NADP(+) conte nt increased (260%) between 1-2 h and returned to control at 4 h. Skin cell NADP(+) increases may be indicative of an early phase of cellula r oxidative stress that may contribute to HD-induced dermal pathogenes is. Since NAD(+) reductions did not precede microvesication and NAM-in duced increases in NAD(+) content did not delay or reduce early cellul ar alterations, the contributory role of NAD(+) to microvesicle format ion may be limited and other biochemical changes should be investigate d.