Analysis of Dose-Response to Hexanal-Induced Gene Expression in A549 Human Alveolar Cells

Abstract

The problems of analyzing dose effects on gene expression are gaining attention in toxicological research. Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and elucidating their modes of toxic action. In the present study, we focused on determining the dose-dependent alterations of gene expression profiles with hexanal exposure and we identified the possible biomarkers of hexanal in A549 human alveolar cells. A549 cells were exposed to a 5% inhibitory concentration (IC5) and a 20% inhibitory concentration (IC20) of hexanal for 48 h. Through microarray analysis using an oligonucleotide chip, we identified that the gene expression patterns were differentially shown in the control group and the hexanal-exposed groups. The hexanal-exposed groups are more sensitive to gene alteration than the control group, and gene expressions are more significantly altered in the IC20 exposure group than in the IC5 exposure group. With clustering analysis of gene expression profiles, we identified 2,929 IC5- and 3,678 IC20-specific genes, and 302 dose-dependently expressed genes. Gene ontology (GO) analysis with 246 annotated genes of the 302 dose-dependent expressed genes showed correlation with the key biological processes involved in neurological system processes, immune system development, cell activation, and cell-cell signaling. In conclusion, current study describes alterations in gene expression profiles in response to exposure to different doses of hexanal and related toxic pathways induced by significantly expressed genes. Moreover, novel genes and pathways that could potentially play a role in the prevention of respiratory disease due to aldehydes are identified.