DNA fragmentation pattern induced in thymocytes by sulphur mustard.
Sulphur mustard (HD) is a blister agent for which no specific therapy exists. The mechanism of cell injury caused by HD is not well understood. This study examined DNA damage in thymocytes exposed to a range of HD concentrations over a time course of 1-24 h. Thymocytes incubated with HD showed an increase in the production of DNA fragments of the type frequently associated with apoptosis, namely, initial formation of large fragments of 30-50, 200-300 and > 700 kilobase pairs (kbp), followed by further degradation to produce an internucleosomal 'ladder' of oligomers of approximately 180 base pairs (bp). Pulsed field electrophoresis analysis of thymocytes incubated with HD detected breakdown of the chromatin up to 3 h before a corresponding increase in the low molecular weight (MW) oligonucleosomal fragments could be seen on conventional agarose gels. These results suggest that cells damaged by HD poisoning may be irretrievably committed to cell death sooner after exposure than previous studies suggested. The nature of the DNA fragments produced suggested that apoptosis may represent a component of the pathway of cell death induced by HD. These aspects may have implications for the search for specific therapeutic reagents effective in the prevention or treatment of HD poisoning.
Michaelson
S
S
Aeronautical and Maritime Research Laboratory, Combatant Protection and Nutrition Branch, Melbourne, Vic., Australia.
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005260:Female; D009151:Mustard Gas / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
D003907:Dexamethasone; D004247:DNA; D009151:Mustard Gas