, Volume 335, Issue 1-2, pp 223-234
Date: 26 Sep 2009

Blood gene expression markers to detect and distinguish target organ toxicity

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

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).

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.