Hypothermia reduces sulphur mustard toxicity.
The effect of temperature on the development of sulphur mustard (HD)-induced toxicity was investigated in first passage cultures of human skin keratinocytes and on hairless guinea pig skin. When cells exposed to HD were incubated at 37 degrees C, a concentration-dependent decline in viability was observed that was maximal by 2 days. In contrast, no significant HD-induced toxicity was evident up to 4 days posttreatment when the cells were incubated at 25 degrees C. However, these protective effects were lost by 24 h when the cells were switched back to 37 degrees C. The protective effects of hypothermia were also demonstrated when apoptotic endpoints were examined. The HD concentration-dependent induction of fragmented DNA (as quantitated using soluble DNA and the TUNEL reaction), morphology, and p53 expression were all significantly depressed when cell cultures were incubated at 25 degrees C compared to 37 degrees C. When animals were exposed to HD vapour for 2, 4, and 6 min and left at room temperature, lesions were produced whose severity was dependent on exposure time and that were maximal by 72 h posttreatment. Moderate cooling (5-10 degrees C) of HD exposure sites posttreatment (4-6 h) significantly reduced the severity of the resultant lesions. However, in contrast to the in vitro results, these effects were permanent. It appears that the early and noninvasive act of cooling HD-exposed skin may provide a facile means of reducing the severity of HD-induced cutaneous lesions.
Mi
Lei
L
Kinchyle Enterprises Inc., Medicine Hat, Alberta, Canada.
Gong
Wenrong
W
Nelson
Peggy
P
Martin
Leanne
L
Sawyer
Thomas W
TW
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007036:Hypothermia, Induced; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D009151:Mustard Gas / Q000633:toxicity*; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D002619:Chemical Warfare Agents; D016159:Tumor Suppressor Protein p53; D009151:Mustard Gas