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

Chemical-induced allergy continues to he an important occupational health p roblem. Despite decades of investigation, the molecular mechanisms underlyi ng chemical-induced hypersensitivity and irritancy remain unclear because o f the complex interplay between properties of different chemicals and the i mmune system. In this study, gene expression induced by toluene diisocyanat e (TDI, a primarily IgE-inducing sensitizer). oxazolone (OXA, a cell-mediat ed hypersensitivity inducing sensitizer), or nonanoic acid (NA, a non-sensi tizing irritant) was investigated using gene arrays. Female BALB/c mice wer e 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 RN A extraction and subsequent hybridization to Affymetrix Mu6500 oligonucleot ide arrays. Of the: 6519 genes on the arrays, there were 44, 13. and 51 gen es in the TDI-, OXA-, and NA-exposed samples, respectively. that displayed a minimum of twofold change in expression level relative to the vehicle con trol. There were 32, 19, and 19 genes that were differentially expressed wi th a minimum of twofold change between TDI and OXA, TDI and NA. OXA and NA, respectively. The differentially expressed genes include immune response-r elated genes, transcriptional Factors. signal transducing molecules, and Ex pressed Sequence Tags. Based on the gene array results, candidate gents wer e further evaluated using RT-PCR, There was only about 47% concordance betw een the gene array and RT-PCR results. Published by Elsevier Science B.V.