Molecular and Cellular Biochemistry

, Volume 335, Issue 1, pp 223–234

Blood gene expression markers to detect and distinguish target organ toxicity

Authors

  • Christina Umbright
    • Toxicology and Molecular Biology BranchNational Institute for Occupational Safety and Health
  • Rajendran Sellamuthu
    • Toxicology and Molecular Biology BranchNational Institute for Occupational Safety and Health
  • Shengqiao Li
    • Biostatistics and Epidemiology Branch, Health Effects Laboratory DivisionNational Institute for Occupational Safety and Health
  • Michael Kashon
    • Biostatistics and Epidemiology Branch, Health Effects Laboratory DivisionNational Institute for Occupational Safety and Health
  • Michael Luster
    • Toxicology and Molecular Biology BranchNational Institute for Occupational Safety and Health
    • Toxicology and Molecular Biology BranchNational Institute for Occupational Safety and Health
    • MS 3014, Molecular Carcinogenesis LaboratoryNational Institute for Occupational Safety and Health (NIOSH)
Article

DOI: 10.1007/s11010-009-0272-5

Cite this article as:
Umbright, C., Sellamuthu, R., Li, S. et al. Mol Cell Biochem (2010) 335: 223. doi:10.1007/s11010-009-0272-5

Abstract

The purpose of this study was to investigate whether the expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ toxicity induced by chemicals in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or a neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities. Similarly, administration of methyl parathion (MP) resulted in neurotoxicity in the rats as evidenced from the inhibition of acetyl cholinesterase activity in their blood. Administration of either chemical also resulted in mild hematotoxicity in the rats. Microarray analysis of the global gene expression profile of rat blood identified distinct gene expression markers capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by AP and MP, respectively. Differential expressions of the marker genes for hepatotoxicity and neurotoxicity were detectable in the blood earlier than the appearance of the commonly used clinical markers (serum transaminases and acetyl cholinesterase). The ability of the marker genes to detect hepatotoxicity and neurotoxicity was further confirmed using the blood samples of rats administered additional hepatotoxic (thioacetamide, dimethylnitrobenzene, and carbon tetrachloride) or neurotoxic (ethyl parathion and malathion) chemicals. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively.

Keywords

Blood gene expression Hepatotoxicity Neurotoxicity Toxicity markers

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Copyright information

© Springer Science+Business Media, LLC. 2009