DNA fragmentation in leukocytes following subacute low-dose nerve agent exposure.
The objective of the present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by single-cell gel electrophoresis (comet assay) after exposure to the chemical warfare nerve agent (CWNA), soman, at doses ranging from 0.1 LD50 to 0.4 LD50, once per day for either 5 or 10 days. Post-exposure recovery periods ranged from 0 to 17 days. Leukocytes were imaged from each animal, and the images analyzed by computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA-treated guinea pigs compared with saline-injected control animals at all doses and time points examined. Notably, significantly increased DNA fragmentation was observed in leukocytes 17 days after cessation of soman exposure. Our findings demonstrate that leukocyte DNA fragmentation assays may provide a sensitive biomarker for low-dose CWNA exposure.
Moffett
J R
JR
Division of Neurosciences, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, Maryland 20910-7500, USA.
Price
R A
RA
Anderson
S M
SM
Sipos
M L
ML
Moran
A V
AV
Tortella
F C
FC
Dave
J R
JR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D020552:Comet Assay; D053938:DNA Fragmentation / Q000187:drug effects*; D006168:Guinea Pigs; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D012999:Soman / Q000494:pharmacology*
D015415:Biomarkers; D002619:Chemical Warfare Agents; D012999:Soman