Blood Gene Expression Markers for Target Organ Toxicity

Details

• Personal Author:
  Joseph P ; Kashon M ; Luster M ; Sellamuthu R ; Umbright C
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biological Factors Blood Blood-Borne Pathogens Digestive System Digestive System Diseases Environmental Monitoring Genetics Hazardous Substances Hematologic Diseases Hematologic Tests Hypersensitivity Laboratories Liver Microbiology Nervous System Occupational Health Safety Toxicology

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• Keywords:
  Biological-effects Biological-factors Blood-analysis Bloodborne-pathogens Chemical-hypersensitivity Exposure-assessment Exposure-levels Exposure-methods Genetic-factors Hepatotoxicity Hepatotoxins Laboratory-animals Liver-damage Liver-disorders Microscopic-analysis Microscopy Neuropathology Neurophysiological-effects Neurotoxic-effects Statistical-analysis Toxic-effects Toxicopathology

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035290
• Citation:
  Toxicologist 2009 Mar; 108(1):333
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e8f517faa38e649da63e78f4bad58661c91fc762f8cb0417bdb4098a37a20ed2146031b12575c41bd0f950badebf846b44ea8ba39b9a5c37dfd243bdf2dae63
• Download URL:
  https://stacks.cdc.gov/view/cdc/187198/cdc_187198_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]