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from these sites, as well as from epithelium at the periphery of the injured site. Time for healing varies depending on the degree of tissue injury, residual skin necrosis, and presence or absence of infection.

Scar formation following sulfur mustard injury in specific anatomical areas may be profound and disabling. As has been stated, the genital regions are especially susceptible to sulfur mustard injury. Severe scarring of scrotal and penile tissue can cause deformity and impair sexual performance.

Microscopically, the epidermis and dermis respond adversely to the irritant effects of sulfur mustard. The National Defense Research Committee group at Harvard made an extensive histological study of a large series of experimental sulfur mustard burns of varying severity in human subjects (Renshaw, 1946). Within the epidermis, and within three hours after sulfur mustard dosages that produce erythema, only a few scattered basal cells show nuclear changes consisting of swelling, loss of chromatin, and dispersion of chromatin to the nuclear periphery, clear vesiculation, vacuolization of the cytoplasm around the nucleus, and in some cells vacuolar or hydropic degeneration of the cytoplasm and pyknosis of nuclei. Later, disintegration of the cytoplasmic membrane of basal cells becomes prominent. In some areas, but more often in more severely damaged skin, these degenerative changes may be seen throughout the basal layer of the epidermis.

Ultrastructural studies of human skin have been supplemented with studies of mustard-exposed human skin grafts on athymic nude mice. Ultrastructurally, the type of cellular injury seen in human skin does not appear to differ from that observed subsequent to a wide variety of toxic insults that lead ultimately to epithelial cell degeneration. The sequence of events begins within basal keratinocytes and always within the cell nucleus. Extensive condensation and margination of heterochromatins and loss of euchromatins are followed by blebbing of the nuclear membrane (blebbing of the nuclear membrane is also evident on light microscopy at this stage). Cell lysis begins with the formation of paranuclear vacuoles, swelling of rough and smooth surface endoplasmic reticulum, dissociation of free rosettes of polyribosomes, loss of mitochondrial structure, cytoplasmic vacuolization, and eventual disruption of the plasma membrane.

These changes are probably confined principally to basal cells of the epidermis, because basal cells are the most active metabolic cells, actively and continuously synthesizing nucleic acids and nucleoproteins that are vital for cell growth and division. Antineoplastic agents such as sulfur mustard and nitrogen mustard derivatives exert their most prominent cytotoxic effects on cells that are actively producing large quantities of nucleic acids and nucleoproteins in preparation for cell division. Cross-linking of DNA is one of the most important cytopathic



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