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Blood gene expression markers to detect and distinguish target organ toxicity.

Authors
Umbright-C; Sellamuthu-R; Li-S; Kashon-M; Luster-M; Joseph-P
Source
Mol Cell Biochem 2010 Feb; 335(1-2):223-234
NIOSHTIC No.
20036397
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
Hepatotoxicity; Hepatotoxins; Laboratory-animals; Liver; Liver-damage; Liver-disorders; Neurotoxic-effects; Biomarkers; Author Keywords: Blood gene expression; Hepatotoxicity; Neurotoxicity; Toxicity markers
Contact
P. Joseph, MS 3014, Molecular Carcinogenesis Laboratory, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, 26505 Morgantown, WV, USA
CODEN
MCBIB8
Publication Date
20100201
Document Type
Journal Article
Email Address
pjoseph1@cdc.gov
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Issue of Publication
1-2
ISSN
0300-8177
NIOSH Division
HELD
Source Name
Molecular and Cellular Biochemistry
State
WV
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