Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Bis-(2-chloroethyl) sulfide (sulfur mustard, SM) is a carcinogenic alkylating agent that has been utilized as a chemical warfare agent. To understand the mechanism of SM-induced lung injury, we analyzed global changes in gene expression in a rat lung SM exposure model. Rats were injected in the femoral vein with liquid SM, which circulates directly to the pulmonary vein and then to the lung. Rats were exposed to 1, 3, or 6 mg/kg of SM, and lungs were harvested at 0.5, 1, 3, 6, and 24 h postinjection. Three biological replicates were used for each time point and dose tested. RNA was extracted from the lungs and used as the starting material for the probing of replicate oligonucleotide microarrays. The gene expression data were analyzed using principal component analysis and two-way analysis of variance to identify the genes most significantly changed across time and dose. These genes were ranked byp value and categorized based on molecular function and biological process. Computer-based data mining algorithms revealed several biological processes affected by SM exposure, including protein catabolism, apoptosis, and glycolysis. Several genes that are significantly upregulated in a dose-dependent fashion have been reported as p53 responsive genes, suggesting that cell cycle regulation and p53 activation are involved in the response to SM exposure in the lung. Thus, SM exposure induces transcriptional changes that reveal the cellular response to this potent alkylating agent. Introductionmodification of DNA by SM has been well-characterized Bis-(2-chloroethyl) sulfide (sulfur mustard, SM)1-3 is due to the use of SM and related molecules as anticancer a carcinogen and chemical warfare agent that was used therapies (1), and covalent modification of proteins by on the battlefield during World War I and has since been SM has also been demonstrated (2-5). A variety of used in several conflicts around the globe. SM exposure molecular targets and pathways have been implicated in usedin eveal cnflctsaroud te gobe.SM xpoure the mechanism of toxicity of SM exposure (1); however, results in cutaneous, pulmonary, and ocular injury. th e mechanism s of cexposuremain;undeDespite much research, an effective medical countermeathe precise mechanisms of cellular injury remain undesure for SM exposure has not been developed because lineated. the molecular mechanism of SM toxicity is not wellThe lung is a primary target of SM vapor. Inhalation understood. SM is a potent alkylating agent capable of exposure causes pulmonary...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.