Blood gene expression markers for target organ toxicity.
Joseph-P; Umbright-C; Sellamuthu-R; Kashon-M; Luster-M
Toxicologist 2009 Mar; 108(1):333
The purpose of this study was to investigate whether peripheral blood gene expression can be used as non-invasive, surrogate marker(s) to detect and distinguish target organ toxicity. Rats were intraperitoneally administered a single, acute dose of either a 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. Microarray analysis of the global gene expression profile in rat blood identified distinct gene expression markers which were capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by the chemicals. Differential expressions of the marker genes, for hepatotoxicity and neurotoxicity, were detectable in the blood much earlier than the appearance of the widely used clinical markers corresponding to the respective toxicities. The hepatotoxicity and neurotoxicity marker genes were further validated using additional hepatotoxic (thioacetamide, dimethylnitrobenzene and carbon tetrachloride) or neurotoxic (ethyl parathion, chlorpyrifos and malathion) chemicals. The blood gene expression markers detected and distinguished hepatotoxicity and neurotoxicity induced by the chemicals with significant accuracy and specificity. In summary, our results demonstrated that blood gene expression may be used as markers to detect and distinguish target organ toxicity. Furthermore, it appears that the blood gene expression markers are more sensitive than the traditional toxicity markers. Disclaimer: The findings and conclusions in this abstract have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be constructed to represent any agency determination or policy.
Biological-effects; Biological-factors; Blood-analysis; Bloodborne-pathogens; Chemical-hypersensitivity; Exposure-assessment; Exposure-levels; Exposure-methods; Genetic-factors; Hepatotoxicity; Hepatotoxins; Laboratory-animals; Liver; Liver-damage; Liver-disorders; Microscopic-analysis; Microscopy; Neuropathology; Neurophysiological-effects; Neurotoxic-effects; Statistical-analysis; Toxic-effects; Toxicopathology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland