Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds.
Benzene, toluene, o-xylene, ethylbenzene, trichloroethylene and dichloromethane are the most widely used volatile organic compounds (VOCs), and their toxic mechanisms are still undefined. This study analyzed the genome-wide expression profiles of human promyelocytic leukemia HL-60 cells exposed to VOCs using a 35-K whole human genome oligonucleotide microarray to ascertain potential biomarkers. Genes with a significantly increased expression levels (over 1.5-fold and p-values <0.05) with six VOCs were then classified with gene ontology and KEGG pathway annotation. At IC(20) doses identified genes were functionally categorized as being involved in cytokine-cytokine receptor interactions and the toll-like receptor signaling pathway, whereas exposure at IC(50) doses identified genes associated with the p53 signaling pathway, apoptosis, and natural killer cell-mediated cytotoxicity pathway. Functionally important immune response- and apoptosis-related genes were further validated by real-time RT-PCR. The results showed that IFIT1, IFIT2, IFIT3, USP18, INFGR2, PMAIP1, GADD45A, NFKBIA, TNFAIP3, and BIRC3 genes altered their expression profiles in a dose-dependent manner. Similar expressions profiles were also found in human erythromyeloblastoid leukemia K562 cells and in human leukemic monocyte lymphoma U937 cells. In conclusion, both gene expression profiles and gene ontology analysis have elucidated potential gene-based biomarkers and provided insights into the mechanism underlying the response of human leukemia cell lines to VOC exposure.
Sarma
Sailendra Nath
SN
Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Republic of Korea. sarma@kist.re.kr <sarma@kist.re.kr>
Kim
Youn-Jung
YJ
Ryu
Jae-Chun
JC
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014050:Toluene / Q000494:pharmacology; D020298:U937 Cells; D055549:Volatile Organic Compounds / Q000494:pharmacology*; D014992:Xylenes / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C484290:IFIT1 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D055549:Volatile Organic Compounds; D014992:Xylenes; D014050:Toluene; C026114:2-xylene