Sarma, Sailendra Nath Kim, Youn-Jung Ryu, Jae-Chun 2024-01-20T19:05:04Z 2024-01-20T19:05:04Z 2021-09-01 2010-05-27 0300-483X https://pubs.kist.re.kr/handle/201004/131438 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 IC20 doses identified genes were functionally categorized as being involved in cytokine-cytokine receptor interactions and the toll-like receptor signaling pathway, whereas exposure at IC50 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, INFAIP3, 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved. English ELSEVIER IRELAND LTD NATURAL-KILLER-CELLS INTERFERON-GAMMA HEALTH-RISKS BENZENE INDUCTION INDUSTRY PATHWAYS CANCER FAMILY GROWTH Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds Article 10.1016/j.tox.2010.03.014 1 TOXICOLOGY, v.271, no.3, pp.122 - 130 TOXICOLOGY 271 3 122 130 scie scopus 000278777600008 2-s2.0-77952518374 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article NATURAL-KILLER-CELLS INTERFERON-GAMMA HEALTH-RISKS BENZENE INDUCTION INDUSTRY PATHWAYS CANCER FAMILY GROWTH Gene expression profiles VOCs Toxicity Oligonucleotide microarray Real-time RT-PCR