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Series GSE2950 Query DataSets for GSE2950
Status Public on Dec 22, 2005
Title Microarray analysis of mouse ear tissue exposed to bis-(2-chloroethyl) sulfide
Organism Mus musculus
Experiment type Expression profiling by array
Summary Sulfur mustard (SM) is a potent alkylating agent. We are developing medical countermeasures to reduce the injury caused by SM exposure. Screening in the mouse ear vesicant model has identified three effective compounds: dimercaprol (British anti-lewisite), indomethacin, and octyl homovanillamide (OHV). To identify gene expression changes that correlate with compound efficacy we used oligonucleotide microarrays to compare gene expression profiles in vehicle-exposed skin, SM-exposed skin, and skin pretreated with each compound before SM exposure. Mice were topically exposed on the inner surface of the right ear to SM alone or pretreated for 15 min with one of the compounds and then exposed to SM. Left ears were vehicle-exposed. Ear tissue was harvested 24 hr later for ear weight determination (an endpoint indicating compound efficacy). The exposure groups were: methylene chloride (sulfur mustard vehicle); ethanol (drug vehicle); 0.08 mg sulfur mustard; 6.25 mg dimercaprol 15 min before 0.08 mg sulfur mustard; 1.34 mg indomethacin 15 min before 0.08 mg sulfur mustard; 0.6 mg octylhomovanillamide 15 min before 0.08 mg sulfur mustard; 6.25 mg dimercaprol alone; 1.34 mg indomethacin alone; 0.6 mg octylhomovanillamide alone. RNA was extracted from the tissues and used to generate oligonucleotide microarray probes. Principal component analysis of the gene expression data revealed partitioning of the samples based on drug treatment and SM exposure. Vehicle-exposed mouse ears clustered away from the other treatment groups. SM-exposed mouse ears pretreated with dimercaprol or OHV clustered more closely with vehicle-exposed ears, while SM-exposed mouse ears pretreated with indomethacin clustered more closely with SM-exposed ears. This clustering of the samples is supported by the ear weight data, in which the indomethacin group has ear weights closer to the SM-exposed group, whereas the dimercaprol and OHV groups have ear weights closer to the vehicle-exposed group. Correlation coefficients were calculated for each gene based on the correlation between gene expression level and ear weight. These data provide the basis for understanding what gene expression changes are important in the development of effective SM medical countermeasures.
Keywords: ordered
 
Overall design Exposure of mouse ears to sulfur mustard alone, sulfur mustard preceded by drug treatment, or vehicle compounds. Naïve controls were also included. Biological replicates of at least n=3 were examined for each exposure condition.
 
Contributor(s) Dillman JF, Hege AI, Phillips CS, Orzolek LD, Sylvester AJ, Bossone C, Henemyre-Harris C, Kiser RC, Choi YW, Schlager JJ, Sabourin CL
Citation(s) 16377760
Submission date Jul 15, 2005
Last update date Jan 08, 2019
Contact name James F Dillman
E-mail(s) james.f.dillman2.civ@mail.mil
Phone 4104361723
Organization name U.S. Army Medical Research Institute of Chemical Defense
Department Cell and Molecular Biology Branch
Lab Molecular Toxicology Team
Street address 3100 Ricketts Point Rd
City Aberdeen Proving Ground
State/province MD
ZIP/Postal code 21010-5400
Country USA
 
Platforms (2)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
GPL340 [MOE430B] Affymetrix Mouse Expression 430B Array
Samples (107)
GSM64266 1leftB
GSM64267 1left
GSM64268 1rightB
Relations
BioProject PRJNA92421

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