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Series GSE40795 Query DataSets for GSE40795
Status Public on Oct 12, 2012
Title Transcriptomic Dose Response Changes in Female Mouse and Rat Lungs following Chloroprene Exposure
Organisms Mus musculus; Rattus norvegicus
Experiment type Expression profiling by array
Summary ß-chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of multi-organ tumors in mouse and rat cancer bioassays. A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12.8 ppm while a small, but not statistically significant, increase was observed in female rats only at the highest exposure concentration of 80 ppm. The metabolism of chloroprene results in the generation of reactive epoxides and the rate of overall chloroprene metabolism is highly species dependent. To identify potential key events in the mode-of-action of chloroprene lung tumorigenesis, dose response and time course gene expression microarray measurements were made in the lungs of female mice and female rats. The gene expression changes were analyzed using both a traditional analysis of variance approach followed by pathway enrichment analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross-species differences in tumor incidence and transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day. The closer correspondence of the transcriptional changes with the tumor response are likely due to their reflection of the overall balance between metabolic activation and detoxication reactions whereas the current tissue dose surrogate reflects only oxidative metabolism.
 
Overall design Female mice (B6C3F1/Crl) were exposed to chloroprene (CAS 126-99-8) by whole-body inhalation exposure at 0, 0.3, 2, 13, or 90 ppm. Exposures were performed for 6 hr/day, 5 days per week. The animals were sacrified at 5 days or 19 days (15 exposure days) post initiation of exposure. The right lung was excised and gene expression microarray analysis was performed using Affymetrix Mouse 430_2 arrays. Female rats (F344/NCrl) were exposed to chloroprene (CAS 126-99-8) by whole-body inhalation exposure at 0, 5, 30, 90, or 200 ppm. Exposures were performed for 6 hr/day, 5 days per week. The animals were sacrified at 5 days or 19 days (15 exposure days) post initiation of exposure. The right lung was excised and gene expression microarray analysis was performed using Affymetrix Rat 230_2 arrays.
 
Contributor(s) Thomas RS
Citation(s) 23125180
Submission date Sep 12, 2012
Last update date Feb 11, 2019
Contact name Longlong Yang
E-mail lyang@ciit.org
Phone 919-558-1374
Organization name CIIT Centers for Health Research
Street address 6 Davis Dr.
City RTP
State/province NC
ZIP/Postal code 27709
Country USA
 
Platforms (2)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
GPL1355 [Rat230_2] Affymetrix Rat Genome 230 2.0 Array
Samples (100)
GSM1001775 RT_03_5d_118_Lung_CLPR03_RSTSRP805
GSM1001776 RT_03_5d_119_Lung_CLPR-03_RSTSRP805
GSM1001777 RT_03_5d_120_Lung_CLPR-03_RSTSRP805
Relations
BioProject PRJNA175000

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40795_RAW.tar 344.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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