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Blood gene expression markers to detect and distinguish target organ toxicity

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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.

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Acknowledgments

The authors gratefully acknowledge the valuable help provided by Dr. Krishnan Sriram and Christopher Felton during euthanasia of the rats and blood collection. The critical review of the manuscript by Dr. Victor Johnson is also gratefully acknowledged.

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Authors and Affiliations

  1. Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, WV, USA

    Christina Umbright, Rajendran Sellamuthu, Michael Luster & Pius Joseph

  2. Biostatistics and Epidemiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA

    Shengqiao Li & Michael Kashon

  3. MS 3014, Molecular Carcinogenesis Laboratory, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, 26505, Morgantown, WV, USA

    Pius Joseph

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  1. Christina Umbright
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  2. Rajendran Sellamuthu
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  5. Michael Luster
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Correspondence to Pius Joseph.

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Disclaimer

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

Christina Umbright and Rajendran Sellamuthu contributed equally to this work.

Data deposition

The microarray data have been deposited in the Gene Expression Omnibus (GEO) Database, www.ncbi.nlm.nih.gov/geo (accession number GSE13442).

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Umbright, C., Sellamuthu, R., Li, S. et al. Blood gene expression markers to detect and distinguish target organ toxicity. Mol Cell Biochem 335, 223–234 (2010). https://doi.org/10.1007/s11010-009-0272-5

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  • DOI: https://doi.org/10.1007/s11010-009-0272-5

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