He, B., A.E. Munson, and B.J. Meade. (2000). Microarray Analysis of Gene Expression Patterns Induced by Irritant and Sensitizing Chemicals. The Toxicologist 54(1). Abstract #1429.

toluene diisocyanate - 26472-62-5; oxazolone - 15646-46-5; nonanoic acid - 00112-05-0

Chemical-induced dermatitis continues to be an important occupational health problem. Despite decades of investigation, the molecular mechanisms underlying chemical induced hypersensitivity and irritation remain unclear due to the complicated interplay between properties of different chemicals and the immune system. In this study gene expression patterns induced by toluene diisocyanate (TDI, IgE-inducing sensitizer), oxazolone (OXA, cell-mediated hypersensitivity inducing sensitizer) or nonanoic acid (non-sensitizing irritant) were investigated using gene microarrays. Female BALB/c mice were dermally exposed on the ears once daily for 4 consecutive days. On day 5 the lymph nodes draining the exposure sites were collected and used for mRNA extraction. For TDI and OXA exposures, the concentrations used induced similar quantities of mRNA in the draining lymph nodes. The extracted mRNAs were reverse transcribed into cDNAs and then in vitro transcribed into biotin-labeled cRNAs. The hybridization of labeled cRNAs to GeneChip Mu6500 oligonucleotide arrays (Affymetrix, CA) and scanning were conducted by Research Genetics, Inc. AL. Of the 6500 genes on the arrays, there were 19 genes whose expression levels were significantly different between TDI- and nonanoic acid-treated samples, 18 genes between OXA and nonanoic acid samples and 33 genes between TDI and OXA samples. These include immune response-related genes, transcriptional factors, signal transducing molecules and Expressed Sequence Tags. Microarray analysis identified differentially expressed genes which can be further investigated by conventional methods. Candidate genes will be chosen for further evaluation following exposure to a panel of chemical sensitizers and irritants. Further studies will be conducted to define the functional roles of these genes.