Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model.
Ultrastructural and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) studies were conducted to compare mechanisms of 2-chloroethyl ethyl sulfide (CEES) and heat-induced injury to EpiDerm. Twenty-two hours after 2-h exposure to the monofunctional alkylating agent CEES, budding of cytoplasm, clumping of nuclear chromatin, disintegration of nuclear membranes and cytoplasmic structures, and cytoplasmic vacuolization were detected, especially in the basal cells near the pseudobasement membrane. TUNEL techniques revealed DNA fragmentation distinct from that normally associated with terminal keratinocyte differentiation. Similar evaluations 22.5 h after 90 min exposure of EpiDerm to elevated temperature (45 degrees C) produced a different pattern of cell damage. Swelling of intercellular spaces, extensive cytoplasmic vacuolization, disruption of normal nuclear shape, reduced cell membrane integrity, and release of cellular material in the basal region characterized heat injury. Heat did not alter the DNA fragmentation normally associated with keratinocyte maturation. These data suggest that CEES elicited an apoptotic mechanism of cell death with features of terminal differentiation such as nuclear membrane disintegration and loss of cytoplasmic structures. Heat, alternatively, produced changes more typical of oncotic necrosis.
Blaha
M
M
U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760, USA. michael.blaha@na.amedd.army.mil
Kohl
J
J
DuBose
D
D
Bowers
W
W
Walker
J
J
D017209:Apoptosis / Q000187:drug effects; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity*; D009924:Organ Culture Techniques; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure
C031278:2-chloroethyl ethyl sulfide; D004247:DNA; D009151:Mustard Gas