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

Abstract：

: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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Batal M,Boudry I,Mouret S,Wartelle J,Emorine S,Bertoni M,Bérard I,Cléry-Barraud C,Douki T

doi

10.1016/j.taap.2013.10.010

subject

Has Abstract

pub_date

2013-12-15 00:00:00

pages

644-50

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(13)00449-3

journal_volume

273

pub_type

杂志文章

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