Analysis of mRNA expression profiles highlights alterations in modulation of the DNA damage-related genes under butanal exposure in A549 human alveolar epithelial cells

Abstract

Butanal is a lower-molecular-weight saturated aliphatic aldehyde (LSAA) that is known as one of the important causes of indoor pollution. Although a few studies have been reported, the toxicity of butanal and its underlying mechanisms remain unclear. This study focused on toxicity of butanal with microarray analysis relationships of gene expression patterns between vehicle control and two different concentrations of butanal-treated groups. For a comprehensive examination of butanal effects on gene expression, we exposed human alveolar epithelial (A549) cells to IC5 and IC20 for 48 h and compared the gene expression of treated cells with that of vehicle controls using a human oligonucleotide chip. We identified genes that were changed by more than 1.5-fold through gene expression profile analysis. Transcriptomic profiling indicated different gene expression patterns in vehicle control and butanal-exposed groups and showed that the butanal-exposure group had a higher sensitivity to gene alteration than the control group. Through gene expression profile cluster analysis, we identified 2,998 (1,379 up- and 1,619 down-regulated) in the butanal IC5 groups and 3,200 genes (1,369 up- and 1,831 down-regulated) in the butanal IC20 groups, with 2,710 (1,281 up- and 1,429 down-regulated) specific genes in common. Through Gene Ontology (GO) analysis with these commonly expressed genes reported the several key biological processes which are known as related to DNA damage responses such as "regulation of apoptosis", "regulation of cell proliferation", "immune response", "inflammatory response". We confirmed the functional changes using a cellular assay. Overall, butanal responses are primarily indicative for genotoxicity. This toxicity mechanism is linked to respiratory diseases such as cancer and chronic obstructive pulmonary disease (COPD). The present findings could be important in providing further understanding of the role of aldehydes in the onset of pulmonary diseases.