Browse > Article

Functional Gene Analysis to Identify Potential Markers Induced by Benzene in Two Different Cell Lines, HepG2 and HL-60  

Kim, Youn-Jung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
Song, Mi-Kyung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
Sarma, Sailendra Nath (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
Choi, Han-Saem (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
Ryu, Jae-Chun (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
Publication Information
Molecular & Cellular Toxicology / v.4, no.3, 2008 , pp. 183-191 More about this Journal
Abstract
Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.
Keywords
Volatile organic compounds (VOCs); Benzene; Microarray; Gene ontology;
Citations & Related Records

Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Hirabayashi, Y. et al. Mechanism of benzene-induced hematotoxicity and leukemogenicity: current review with implication of microarray analyses. Toxicol Pathol 32:12-16 (2004)   DOI   ScienceOn
2 Snyder, R. Benzene and leukemia. Crit Rev Toxicol 32:155-210 (2002)   DOI   ScienceOn
3 Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63 (1983)   DOI   ScienceOn
4 Pariselli, F., Sacco, M. G. & Rembges, D. An optimized method for in vitro exposure of human derived lung cells to volatile chemicals. Exp Toxicol Pathol (2008)
5 International Agency for Research on Cancer, Overall evaluations of carcinogenicity, in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans (1987)
6 Snyder, R., Witz, G. & Goldstein, B. D. The toxicology of benzene. Environ Health Perspect 100:293-306 (1993)   DOI
7 Liu, L. et al. The study of DNA oxidative damage in benzene-exposed workers. Mutat Res 370:145-150 (1996)   DOI
8 Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121 (2001)
9 Golding, B. T. & Watson, W. P. Possible mechanisms of carcinogenesis after exposure to benzene. IARC Sci Publ 150:75-88 (1999)
10 Schmidt, P. et al. Hepatotoxicity of benzene, 1,1,2,2- tetrachloroethane and carbon tetrachloride. Z Gesamte Hyg 3:167-172 (1980)
11 Tatsuya, K. et al. Event Ontology: A pathway-centric ontology for biological processes. Pac Symp Biocomput 11:152-163 (2006)
12 Shen, M. et al. Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity. Carcinogenesis 10:2083-2089 (2006)
13 Lamm, S. H. & Grünwald, H. W. Benzene exposure and hematotoxicity. Science 5776:998-999 (2006)
14 Kolachana, P. et al. Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo. Cancer Res 5: 1023-1026 (1993)
15 International Agency for Research on Cancer, Some industrial chemicals and dyestuffs, in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans (1982)
16 Heijne, W. H. et al. Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure. Mutat Res 575:85-101 (2005)   DOI   ScienceOn
17 Perez, C. A. Liver damage in workers exposed to hydrocarbons. Gastroenterol Hepato 6:334-337 (2006)
18 Snyder, R. Benzene's toxicity: a consolidated short review of human and animal studies by HA Khan. Hum Exp Toxicol 9:687-696 (2007)
19 Ashburne, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25-29 (2000)   DOI   ScienceOn
20 Gist, G. L. and Burg, J. R. Benzene-a review of the literature from a health effects perspective. Toxicol Ind Health 13:661-714 (1997)   DOI
21 Te Pas, M. F. et al. Biochemical pathways analysis of microarray results: regulation of myogenesis in pig. BMC Dev Biol 7:66-80 (2007)   DOI
22 Bogadi-Sare, A. & Zavali'c, M. Toxic effects of benzene and toluene. Lijec Vjesn 125:28-30 (2003)