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Publication : Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin.

First Author  Batal M Year  2013
Journal  Toxicol Appl Pharmacol Volume  273
Issue  3 Pages  644-50
PubMed ID  24141030 Mgi Jnum  J:205209
Mgi Id  MGI:5544372 Doi  10.1016/j.taap.2013.10.010
Citation  Batal M, et al. (2013) Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin. Toxicol Appl Pharmacol 273(3):644-50
abstractText  Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM-DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM-DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker.
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