PMID- 22302311
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20201209
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 126
IP  - 2
DP  - 2012 Apr
TI  - Differential gene expression responses distinguish contact and respiratory 
      sensitizers and nonsensitizing irritants in the local lymph node assay.
PG  - 413-25
LID - 10.1093/toxsci/kfs071 [doi]
AB  - 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 ((3)HTdR) 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.
FAU - Adenuga, David
AU  - Adenuga D
AD  - Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 
      Midland, Michigan 48674, USA.
FAU - Woolhiser, Michael R
AU  - Woolhiser MR
FAU - Gollapudi, B Bhaskar
AU  - Gollapudi BB
FAU - Boverhof, Darrell R
AU  - Boverhof DR
LA  - eng
PT  - Journal Article
DEP - 20120202
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Irritants)
RN  - 101-86-0 (hexyl cinnamic aldehyde)
RN  - 7864XYD3JJ (Acrolein)
SB  - IM
MH  - Acrolein/*analogs & derivatives/toxicity
MH  - Animals
MH  - Dinitrochlorobenzene/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - *Gene Expression Profiling
MH  - Irritants/*toxicity
MH  - Lymph Nodes/*drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oligonucleotide Array Sequence Analysis
MH  - Real-Time Polymerase Chain Reaction
MH  - Respiratory System/*drug effects
EDAT- 2012/02/04 06:00
MHDA- 2012/07/17 06:00
CRDT- 2012/02/04 06:00
PHST- 2012/02/04 06:00 [entrez]
PHST- 2012/02/04 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - kfs071 [pii]
AID - 10.1093/toxsci/kfs071 [doi]
PST - ppublish
SO  - Toxicol Sci. 2012 Apr;126(2):413-25. doi: 10.1093/toxsci/kfs071. Epub 2012 Feb 2.