Impact of topical application of XXXX mustard on mice skin and distant organs DNA repair enzyme signature.

@entity25469 @entity32 @entity137 @entity3625 @entity599
UNASSIGNED: @entity599 mustard (SM) is a chemical warfare agent that, upon topical application, damages skin and reaches internal organs through diffusion in blood. Two major toxic consequences of SM exposure are @entity32 , associated with oxidative stress, and the formation of alkylated DNA bases. In the present study, we investigated the impact of exposure to SM on DNA repair, using two different functional DNA repair assays which provide information on several Base Excision Repair (BER) and Excision/Synthesis Repair (ESR) activities. BER activities were reduced in all organs as early as 4h after exposure, with the exception of the defense systems against @entity25469 and @entity3625 which were stimulated. Interestingly, the resulting BER intermediates could activate @entity32 signals, aggravating the @entity32 triggered by SM exposure and leading to increased oxidative stress. ESR activities were found to be mostly inhibited in skin, brain and kidneys. In contrast, in the lung there was a general increase in ESR activities. In summary, exposure to SM leads to a significant decrease in DNA repair in most organs, concomitant with the formation of DNA damage. These synergistic genotoxic effects are likely to participate in the high @entity137 of this alkylating agent. Lungs, possibly better equipped with repair enzymes to handle exogenous exposure, are the exception.
