, Volume 18, Issue 6, pp 715–721 | Cite as

Transcriptional toxicity of the Yangtze River source water on mouse (Mus musculus) detected by cDNA microarray

  • Bing Wu
  • Shupei Cheng
  • Yiqiang Li
  • Jie Kong
  • Dayong Zhao
  • Yan Zhang
  • Xuxiang Zhang


In order to assess the potential health effects of source water from the Yangtze River at Nanjing section, China, hepatic transcriptional profiles of male mice (Mus musculus) exposed to source water for 90 days were measured with Affymetrix Mouse Genome 430A 2.0 Array. A total of 585 gene expressions were significantly altered (1.5-fold, P ≤ 0.05), including 298 up-regulated genes and 287 down-regulated genes. Among the identified genes, potentially important genes that may be implicated in the liver cancer were found, including VCAM 1, Dusp1, Cyp7a1, Egfr and Fhit. The source water exposure also resulted in significant aberration of gene expressions and biological pathways linking to xenobiotic metabolism, signal transduction, cell growth and death, immune/inflammation response and oxidative stress response. The results provide excellent insights into early toxic effects of the Yangtze River source water on human and environmental health.


Yangtze River Source water Mus musculus Transcriptional toxicity Genechip 



This research work was financially supported by Engineering Center of Water treatment and Environment Remediation at National Education Ministry of China (WTWER0720), Department of Science and Technology for Jiangsu Province of China (BZ2007064) and The Environmental Monitoring Center of Jiangsu Province (0711).


  1. Ahlborn GJ, Nelson GM, Ward WO, Knapp G, Allen JW, Ouyang M, Roop BC, Chen Y, O’Brien T, Kitchin KT, Delker DA (2008) Dose response evaluation of gene expression profiles in the skin of K6/ODC mice exposed to sodium arsenite. Toxicol Appl Pharmacol 227:400–416. doi: 10.1016/j.taap.2007.10.029 CrossRefGoogle Scholar
  2. Amor VM, de Caceres I, Bandres E, Orgaz JL, Sanchez-Perez I, Cuenca BJ, Garcia-Fondillas J, Perona R (2008) Identification of DUSP1/MKP1 mediated pathways in lung cancer progression. Lyon, France, pp 69–70Google Scholar
  3. Anderson K, Andrews R, Yin L, McLeod R, MacDonald C, Hayes JD, Grant MH (1998) Cytotoxicity of xenobiotics and expression of glutathione-S-transferases in immortalised rat hepatocyte cell lines. Hum Exp Toxicol 17:131–137. doi: 10.1191/096032798678908404 CrossRefGoogle Scholar
  4. Andrew AS, Bernardo V, Warnke LA, Davey JC, Hampton T, Mason RA, Thorpe JE, Ihnat MA, Hamilton JW (2007) Exposure to arsenic at levels found in U.S. drinking water modifies expression in the mouse lung. Toxicol Sci 100:75–87. doi: 10.1093/toxsci/kfm200 CrossRefGoogle Scholar
  5. Bromberg J (2002) Stat proteins and oncogenesis. J Clin Invest 109:1139–1142Google Scholar
  6. Conlin A, Steele RJC, Wolf CR (2008) Dusp1/mkp-1, dusp2/hpac1 and dusp8/vh5 expression in colorectal cancer. Brimingham, England, p 349Google Scholar
  7. Crosby LM, Simmons JE, Ward WO, Moore TM, Morgan KT, DeAngelo AB (2008) Integrated disinfection by-products (DBP) mixtures research: gene expression alterations in primary rat hepatocyte cultures exposed to DBP mixtures formed by chlorination and ozonation/postchlorination. J Toxicol Environ Health Part A 71:1195–1215CrossRefGoogle Scholar
  8. De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello MR, Aldinucci D, Pinto A, Normanno N (2008) The role of the EGFR signaling in tumor microenvironment. J Cell Physiol 214:559–567. doi: 10.1002/jcp.21260 CrossRefGoogle Scholar
  9. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen GH, Mukherjee C, Shi YF, Gelinas C, Fan YJ, Nelson DA, Jin SK, White E (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51–64. doi: 10.1016/j.ccr.2006.06.001 CrossRefGoogle Scholar
  10. Dong F, Mei ZH, Lou X (2001) Research of genetic toxicity of organic pollutants in source water and drinking water in Nanjing. Environ Monit China 17:2–7Google Scholar
  11. Foja S, Goldberg M, Schagdarsurengin U, Dammann R, Tannapfel A, Ballhausen WG (2005) Promoter methylation and loss of coding exons of the fragile histidine triad (FHIT) gene in intrahepatic cholangiocarcinomas. Liver Int 25:1202–1208. doi: 10.1111/j.1478-3231.2005.01174.x CrossRefGoogle Scholar
  12. Forsberg L, de Faire U, Morgenstern R (2001) Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 389:84–93. doi: 10.1006/abbi.2001.2295 CrossRefGoogle Scholar
  13. Garrett MA (2001) Cell cycle control and cancer. Curr Sci 81:515–522Google Scholar
  14. Gatzidou ET, Zira AN, Theocharis SE (2007) Toxicogenomics: a pivotal piece in the puzzle of toxicological research. J Appl Toxicol 27:302–309. doi: 10.1002/jat.1248 CrossRefGoogle Scholar
  15. Giehl K, Menke A (2008) Microenvironmental regulation of E-cadherin-mediated adherens junctions. Front Biosci 13:3975–3985. doi: 10.2741/2985 CrossRefGoogle Scholar
  16. Hagiwara T, Kono S, Yin G, Toyomura K, Nagano J, Mizoue T, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya F, Imaizumi N (2005) Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: the Fukuoka colorectal cancer study. Cancer Res 65:2979–2982. doi: 10.1158/0008-5472.CAN-04-3872 CrossRefGoogle Scholar
  17. Hoyt PR, Doktycz MJ, Beattie KL, Greeley MS (2003) DNA microarrays detect 4-nonylphenol-induced alterations in gene expression during zebrafish early development. Ecotoxicology 12:469–474. doi: 10.1023/B:ECTX.0000003032.14044.c8 CrossRefGoogle Scholar
  18. Kamezaki S, Kurozawa Y, Iwai N, Hosoda T, Okamoto M, Nose T (2005) Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer. Eur J Cancer 41:2355–2359. doi: 10.1016/j.ejca.2005.07.005 CrossRefGoogle Scholar
  19. Kawano T, Yanoma S, Nakamura Y, Shiono O, Kokatu T, Kubota A, Furukawa M, Tsukuda M (2005) Evaluation of soluble adhesion molecules CD44 (CD44st, CD44v5, CD44v6), ICAM-1, and VCAM-1 as tumor markers in head and neck cancer. Am J Otolaryngol 26:308–313. doi: 10.1016/j.amjoto.2005.02.005 CrossRefGoogle Scholar
  20. Keshava C, Divi RL, Einem TL, Richardson DL, Leonard SL, Keshova N, Poirier MC, Weston A (2009) Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells. Environ Mol Mutagen 50:134–144. doi: 10.1002/em.20449 CrossRefGoogle Scholar
  21. Li YQ, Wu YL, Chen YG, Kong ZM (2006) Genotoxicity evaluation and a primary risk assessment of organic pollutants in the drinking water sources of Nanjing, China. J Environ Sci (China) 18:983–988. doi: 10.1016/S1001-0742(06)60026-0 Google Scholar
  22. Lin E, Calvano SE, Lowry SF (2000) Inflammatory cytokines and cell response in surgery. Surgery 127:117–126. doi: 10.1067/msy.2000.101584 CrossRefGoogle Scholar
  23. Liu YX, Wang JL, Guo JF, Wu JJ, Lieberman HB, Yin YX (2008) DUSP1 is controlled by p53 during the cellular response to oxidative stress. Mol Cancer Res 6:624–633. doi: 10.1158/1541-7786.MCR-07-2019 CrossRefGoogle Scholar
  24. Mei N, Guo L, Tseng J, Dial SL, Liao W, Manjanatha MG (2008) Gene expression changes associated with xenobiotic metabolism pathways in mice exposed to acrylamide. Environ Mol Mutagen 49:741–745. doi: 10.1002/em.20429 CrossRefGoogle Scholar
  25. Miracle AL, Toth GP, Lattier DL (2003) The path from molecular indicators of exposure to describing dynamic biological systems in an aquatic organism: microarrays and the fathead minnow. Ecotoxicology 12:457–462. doi: 10.1023/B:ECTX.0000003030.67752.04 CrossRefGoogle Scholar
  26. Moreau A, Vilarem MJ, Maurel P, Pascussi JM (2008) Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 5:35–41. doi: 10.1021/mp700103m CrossRefGoogle Scholar
  27. Muller B, Berg M, Yao ZP, Zhang XF, Wang D, Pfluger A (2008) How polluted is the Yangtze River? Water quality downstream from the Three Gorges Dam. Sci Total Environ 402:232–247. doi: 10.1016/j.scitotenv.2008.04.049 CrossRefGoogle Scholar
  28. N’Jai AU, Means JC (2004) Analysis of changes in gene expression in rat liver after benzo(a)pyrene exposure assessed by affymetrix microarray and real-time PCR. 35th annual meeting of the Environmental-Mutagen-Society, Pittsburgh, PA, p 127Google Scholar
  29. Niessen CM (2007) Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 127:2525–2532. doi: 10.1038/sj.jid.5700865 CrossRefGoogle Scholar
  30. Rothlein R, Czajkowski M, Oneill MM, Marlin SD, Mainolfi E, Merluzzi VJ (1988) Induction of intercellular-adhesion molecule-1 on primary and continuous cell-lines by pro-inflammatory cytokines—regulation by pharmacologic agents and neutralizing antibodies. J Immunol 141:1665–1669Google Scholar
  31. Sen B, Mahadevan B, DeMarini DM (2007) Transcriptional responses to complex mixtures—a review. Mutat Res Rev Mutat Res 636:144–177. doi: 10.1016/j.mrrev.2007.08.002 Google Scholar
  32. Silva HC, Garcao F, Coutinho EC, De Oliveira CF, Regateiro FJ (2006) Soluble VCAM-1 and E-selectin in breast cancer: relationship with staging and with the detection of circulating cancer cells. Neoplasma 53:538–543Google Scholar
  33. Snell TW, Brogdon SE, Morgan MB (2003) Gene expression profiling in ecotoxicology. Ecotoxicology 12:475–483. doi: 10.1023/B:ECTX.0000003033.09923.a8 CrossRefGoogle Scholar
  34. Srivastava A, Pandey SN, Choudhuri G, Mittal B (2008) Role of genetic variant A-204C of cholesterol 7 alpha-hydroxylase (CYP7A1) in susceptibility to gallbladder cancer. Mol Genet Metab 94:83–89. doi: 10.1016/j.ymgme.2007.11.014 CrossRefGoogle Scholar
  35. Sun C, Dong Y, Xu S, Yao S, Dai J, Han S, Wang L (2002) Trace analysis of dissolved polychlorinated organic compounds in the water of the Yangtse River (Nanjing, China). Environ Pollut 117:9–14. doi: 10.1016/S0269-7491(01)00169-5 CrossRefGoogle Scholar
  36. Yeung LWY, Guruge KS, Yamanaka N, Miyazaki S, Lam PKS (2007) Differential expression of chicken hepatic genes responsive to PFOA and PFOS. Toxicology 237:111–125. doi: 10.1016/j.tox.2007.05.004 CrossRefGoogle Scholar
  37. Yu H, Jove R (2004) The stats of cancer—new molecular targets come of age. Nat Rev Cancer 4:97–105. doi: 10.1038/nrc1275 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Bing Wu
    • 1
  • Shupei Cheng
    • 1
  • Yiqiang Li
    • 2
  • Jie Kong
    • 1
  • Dayong Zhao
    • 1
  • Yan Zhang
    • 1
  • Xuxiang Zhang
    • 1
  1. 1.State Key Laboratory of Pollution Control and Resource Reuse, School of the EnvironmentNanjing UniversityNanjingChina
  2. 2.Environmental Monitoring Center of Jiangsu ProvinceNanjingChina

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