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Toxicology

Title:		Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds
Author(s):		Sarma SN; Kim YJ; Ryu JC;
Address:		"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 "
Journal Title:		Toxicology
Year:		2010
Volume:		20100330
Issue:		3
Page Number:		122 - 130
DOI:		10.1016/j.tox.2010.03.014
ISSN/ISBN:		1879-3185 (Electronic) 0300-483X (Linking)
Abstract:		"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"
Keywords:		"Adaptor Proteins, Signal Transducing Apoptosis/genetics Carrier Proteins/genetics Cell Line, Tumor Female Gene Expression Profiling/*methods Genome, Human HL-60 Cells Humans K562 Cells Leukemia, Promyelocytic, Acute/*genetics/metabolism/pathology Oligonuc;"
Notes:		"MedlineSarma, Sailendra Nath Kim, Youn-Jung Ryu, Jae-Chun eng Research Support, Non-U.S. Gov't Ireland 2010/04/03 Toxicology. 2010 May 27; 271(3):122-30. doi: 10.1016/j.tox.2010.03.014. Epub 2010 Mar 30"