Dichloromethane (DCM, methylene chloride) can readily absorb and metabolized to several metabolites in different target organs. Several mutagenesis studies and animal bioassays have been demonstrated the carcinogenicity of DCM. In this present study, we analyze the genome wide expression profiles of DCM using human promyelocytic leukemia HL60 cells. Exposure to IC20 and IC50 doses concentration of DCM altered the expression of 1117 and 1684 upand also 730 and 1736 down-regulated genes individually, 366 up- and 281 down-regulated genes were commonly expressed. Genes with a significantly altered the expression levels (over 1.5 fold and p-values<0.05) were then classified with gene ontology (GO) and KEGG pathway annotation. Clustering of differentially expressed common genes were associated with JAKSTAT signaling pathway, MAPK signaling pathway, apoptosis, prostate cancer and small cell lung cancer. GO analysis showed the category wise biological process ontology. Functionally important immune response and apoptosis related genes were also validating their expression profiles by quantitative real-time RTPCR. DCM exposure induces IFN-related genes as part of the immune response which was then followed the apoptosis pathway. GO and KEGG pathway database analyses provided a valuable mechanistic insight of DCM exposure in human leukemia cells.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Olvera-Bello, A. et al. Susceptibility to the cytogenetic effects of dichloromethane is related to the glutathione S-transferase theta phenotype. Toxicol. Lett. 199, 218–224 (2010).
Kim, J.K. et al. Identification of characteristic molecular signature for volatile organic compounds in peripheral blood of rat. Toxicol. Appl. Pharmacol. 250, 162–169 (2011).
IARC. Dry cleaning, some chlorinated solvents and other industrial chemicals. IARC Monogr. Eval. Carcinog. Risks Hum. 63, 74–158 (1995).
IARC. Dichloromethane. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans. Vol. 71. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. Lyon, France: International Agency for Research on Cancer, pp. 251–315 (1999).
Cooper, G.S. et al. Insights from epidemiology into dichloromethane and cancer risk. Int. J. Environ. Res. Public Health 8, 3380–3398 (2011).
Kim, A.S., Eastmond, D.A. & Preston, R.J. Childhood acute lymphocytic leukemia and perspectives on risk assessment of early-life stage exposures. Mutat. Res. 613, 138–160 (2006).
Colt, J.S. & Blair, A. Parental occupational exposures and risk of childhood cancer. Environ. Health Perspect. 106 (Suppl 3), 909–925 (1998).
Hisham, K. et al. Toxicogenomics: principles and applications. Environ. Health Perspect. 112, A962 (2004).
Choi, H.S., Kim, Y.J., Song, M., Song, M.K. & Ryu, J.C. Genotoxicity of nano-silica in mammalian cell lines. Tox. Environ. Health Sci. 3, 7–13 (2011).
Sarma, S.N., Song, M., Kim, Y.J. & Ryu, J.C. Genomewide identification of ethylbenzene and trichloroethylene-regulated genes in human promyelocytic leukemia HL-60 cells. BioChip J. 5, 19–26 (2011).
Bhattacharya, S. & Coghlan, A. One drug, six men, disaster, New Sci. 189, 10–11 (2006).
NRC, Toxicity testing in the 21st century a vision and a strategy, National Academy Press, Washington, DC (2007).
NRC, Application of toxicogenomic technologies to predictive toxicology and risk assessment, National Academy Press, Washington, DC (2007).
Sarma, S.N., Kim, Y.J. & Ryu, J.C. Induction of apoptosis in human leukemia cells through the production of reactive oxygen species and activation of HMOX1 and Noxa by benzene, toluene, and o-xylene. Toxicology 280, 109–117 (2011).
Song, M.K., Kim, Y.J., Song, M. & Ryu, J.C. Gene expression analysis identifies potential biomarkers of phenanthrene in human hepatocytes (HepG2). Tox. Environ. Health Sci. 3, 30–38 (2011).
Kim, Y.J., Kim, E.Y. & Ryu, J.C. Identification of estrogenic genes responding to pathalate esters treatment in human MCF-7 cells. Mol. Cell. Toxicol. 7, 167–174 (2011).
Foa, P. et al. Growth pattern of the human promyelocytic leukaemia cell line HL60. Cell. Tissue Kinet. 15, 399–404 (1982).
Kushida, T., Takagi, T. & Fukuda, K.I. Event ontology: a pathway-centric ontology for biological processes. Pac. Symp. Biocomput. 11, 152–163 (2006).
Te Pas, M.F. et al. Biochemical pathways analysis of microarray results: regulation of myogenesis in pig. BMC Dev. Biol. 7, 66–80 (2007).
Kanehisa, M. et al. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 34, D354–357 (2006).
Lan, Q. et al. Polymorphisms in cytokine and cellular adhesion molecule genes and susceptibility to hematotoxicity among workers exposed to benzene. Cancer Res. 65, 9574–9581 (2005).
Sarma, S.N., Kim, Y.J. & Ryu, J.C. Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds. Toxicology 271, 122–130 (2010).
Kristen, B.O. et al. Stress-activated kinase pathway alteration is a frequent event in bladder cancer. http://dx.doi.org/10.1016/j.urolonc.2010.03.002 (2011).
Suzuki, S. et al. Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells. Cancer Sci. 100, 759–769 (2009).
Tsai, K.N. et al. Cytotoxic effect of recombinant Mycobacterium tuberculosis CFP-10/ESAT-6 protein on the crucial pathways of WI-38 cells. J. Biomed. Biotechnol. 2009, 917084 (2009).
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Meth. 65, 55–63 (1983).
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).
About this article
Cite this article
Sarma, S.N., Han, T., Ryu, JC. et al. Genome-wide analysis of dichloromethane-regulated genes in human promyelocytic leukemia HL-60 cells. BioChip J 6, 65–72 (2012). https://doi.org/10.1007/s13206-012-6109-4
- Gene expression profiles
- Gene ontology
- KEGG pathway