title: Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity.
abstract: In the current study, we aimed to investigate the transcriptomic responses and identify specific molecular signatures of low-molecular-weight saturated aliphatic aldehydes (LSAAs). To evaluate the change in gene expression levels, A549 human alveolar epithelial cells were exposed to six LSAAs (propanal, butanal, pentanal, hexanal, heptanal, and octanal) for 48 h. Clustering analysis of gene expression data show that the low carbon number group (LCG; propanal, butanal, and pentanal) was distinguished from the high carbon number group (HCG; hexanal, heptanal, and octanal). Also, transcriptomic profiling indicates that the LCG exposure group was more sensitive in gene alterations than the HCG group. Supervised analysis revealed 703 LCG specific genes and 55 HCG specific genes. After gene ontology (GO) analysis on LCG specific genes, we determined several key pathways which are known as being related to increase pulmonary toxicity such as cytokine-cytokine receptor interaction and chemokine signaling pathway. However, we did not find pulmonary toxicity-related pathways through GO analysis on HCG specific genes. Genes that are expressed in only the low carbon LSAA exposure group were regarded as biomarkers of aldehyde-induced pulmonary toxicity. In conclusion, this study describes changes in gene expression profiles in the in vitro respiratory system in response to exposure to 6 LSAAs with different carbon numbers and relates these gene alterations to pulmonary toxicity-related pathways. Moreover, novel carbon number-specific genes and pathways can be more widely implemented in combination with the traditional technique for assessment and prediction of exposure to environmental toxicants.
authors.affiliation: Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology P.O. Box 131, Cheongryang, Seoul 130-650, Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Song
authors.forename: Han-Seam
authors.initials: HS
authors.lastname: Choi
authors.forename: Hyo-Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Jae-Chun
authors.initials: JC
authors.lastname: Ryu
mesh_terms: D000447:Aldehydes / Q000737:chemistry* / Q000633:toxicity; D002244:Carbon / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000447:Aldehydes; D018925:Chemokines; D016207:Cytokines; D018121:Receptors, Cytokine; D002244:Carbon