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The role of homologous recombination in the cellular response to sulphur mustard

Lookup NU author(s): Dr Paul Jowsey, Professor Faith Williams, Professor Peter Blain


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Sulphur mustard (SM) is a blistering agent that has been used several times as a weapon during military conflict. Interest in this compound persists due to its ease of production and potential threat as an agent of warfare/terrorism. In addition, there are increasing reports of long-term health effects in individuals previously exposed to this compound, including an increased incidence of certain cancers. It is therefore important to elucidate the toxic mechanisms of SM and how the cell responds to any damage produced. This will allow for better healthcare planning in the event of an exposure and aid in the development of a therapeutic strategy, which is currently lacking. SM is a bifunctional alkylating agent, producing both DNA monoadducts and crosslinks, although the cellular response to these lesions is not well understood. This study aimed to investigate the DNA repair pathways employed by cells exposed to SM. It was found that DNA double strand breaks were generated after SM exposure and cells lacking the homologous recombination DNA repair pathway were more sensitive to the toxicity of SM than wild type cells. Finally, we demonstrate that chemical activation of the HR protein RAD51 offers cellular protection against SM toxicity and thus could be a novel target for therapeutic intervention. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Publication metadata

Author(s): Jowsey PA, Williams FM, Blain PG

Publication type: Article

Publication status: Published

Journal: Toxicology Letters

Year: 2010

Volume: 197

Issue: 1

Pages: 12-18

Print publication date: 01/08/2010

ISSN (print): 0378-4274

ISSN (electronic): 1879-3169

Publisher: Elsevier


DOI: 10.1016/j.toxlet.2010.04.020


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