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- Title
Differential Gene Expression Responses Distinguish Contact and Respiratory Sensitizers and Nonsensitizing Irritants in the Local Lymph Node Assay.
- Authors
Adenuga, David; Woolhiser, Michael R.; Gollapudi, B. Bhaskar; Boverhof, Darrell R.
- Abstract
Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine (3HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA.
- Subjects
GENE expression; CELL differentiation; ALLERGENS; IRRITANTS (Drugs); LYMPH nodes; TOXICOGENOMICS; BIOLOGICAL assay
- Publication
Toxicological Sciences, 2012, Vol 126, Issue 2, p413
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kfs071