Subacute Low Dose Nerve Agent Exposure Causes Dna Fragmentation in Guinea Pig Leukocytes

The objective of present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per day for 10 days. Post-exposure recovery periods were 0, 17 or 110 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 as compared with saline injected control animals at all doses at 0 and 17 days post-exposure periods. Notably, significantly increased DNA fragmentation was observed in leukocytes 17 days after cessation of soman exposure. However, no significant DNA fragmentation was observed at 110 days post-exposure. Our findings demonstrate that leukocyte DNA fragmentation assays may provide a sensitive biomarker for low dose CWNA exposure.