boxylic acid cycle substrates, and oxidative phosphorylation (Squibb and Fowler, 1983). An alternative and as yet unproven theory of Lewisite toxicity postulates inhibition of glycolysis secondary to arsenical inhibition of the hexokinase enzyme. The resultant inhibition of each of the subsequent biochemical steps in energy metabolism leads to energy depletion and cell death.
Animal studies of sulfur mustard effect on skin have been directed principally at defining a role for this agent in the process of carcinogenesis (Fox and Scott, 1980; Heston, 1953; McNamara et al., 1975). Such studies have been performed in a variety of animals including dogs, guinea pigs, rabbits, rats, and mice, as described in Chapter 6. Although several routes of administration have been used, subcutaneous injection of fairly large dosages of sulfur mustard was the most successful route producing cutaneous papillomas and sarcomas. Long-term exposure to sulfur mustard vapor also produced squamous cell and basal cell cancers in rats. These experiments, although crude, suggest that similar acute and chronic exposure in humans may be carcinogenic.
The persistence of lesions following sulfur mustard exposure is directly related to the duration and severity of the exposure. Secondary infection will often influence the process of healing and, in turn, may influence the eventual outcome of skin injury. Injury that results in erythema and edema without vesicle formation is almost always followed by complete healing and no residual cutaneous defects. Sites characterized by early and diffuse hyperpigmentation are exceptions. In such sites, erythema may be followed by exfoliation and skin necrosis. Blistering wounds and necrotic wounds, which characteristically leave large areas of skin devoid of protective epithelium, melanocyte, and intact adnexal structures, are often followed by permanent residual skin defects. Skin damage is intensified in the presence of secondary bacterial infection of unepithelialized skin. The effect of infection is intensified by the action of systemically absorbed sulfur mustard on bone marrow. Intense skin exposure sufficient to cause severe vesiculation and skin necrosis is almost always associated with systemic toxicity. Destroyed or diminished bone marrow activity denotes reduced numbers of or destruction of replicating marrow stem cells (also see Chapter 10).