Analysis of gene expression induced by irritant and sensitizing chemicals using oligonucleotide arrays

Chemical-induced allergy continues to he an important occupational health problem. Despite decades of investigation, the molecular mechanisms underlying chemical-induced hypersensitivity and irritancy remain unclear because of the complex interplay between properties of different chemicals and the immune system. In this study, gene expression induced by toluene diisocyanate (TDI, a primarily IgE-inducing sensitizer). oxazolone (OXA, a cell-mediated hypersensitivity inducing sensitizer), or nonanoic acid (NA, a non-sensitizing irritant) was investigated using gene arrays. 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 RNA extraction and subsequent hybridization to Affymetrix Mu6500 oligonucleotide arrays. Of the: 6519 genes on the arrays, there were 44, 13. and 51 genes in the TDI-, OXA-, and NA-exposed samples, respectively. that displayed a minimum of twofold change in expression level relative to the vehicle control. There were 32, 19, and 19 genes that were differentially expressed with a minimum of twofold change between TDI and OXA, TDI and NA. OXA and NA, respectively. The differentially expressed genes include immune response-related genes, transcriptional Factors. signal transducing molecules, and Expressed Sequence Tags. Based on the gene array results, candidate gents were further evaluated using RT-PCR, There was only about 47% concordance between the gene array and RT-PCR results. Published by Elsevier Science B.V.