Project name: Rattus norvegicus

Description: The purpose of this study was to investigate whether expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ-specific chemical toxicity in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) or methyl parathion (MP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities or neurotoxicity as evidenced from the inhibition of acetyl cholinesterase activity in the blood, respectively. 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 specific for hepatotoxicity and neurotoxicity were detectable in the blood much earlier than the appearance of the commonly used clinical markers, serum transaminases and acetyl cholinesterase. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively and with higher sensitivity than traditional surrogate markers.Keywords: blood, acetaminophen, methyl parathion, rat, hepatotoxicity, neurotoxicityOverall design: 38 samples were analyzed in this experiment. 15 rats were intraperitoneally administered acetaminophen (AP), 15 rats were intraperitoneally administered methyl parathion (MP), and 8 rats were intraperitoneally administered vegetable oil. At time intervals of 4, 12, and 24 hours following administration of acetaminophen or methyl parathion, 4 rats per chemical were sacrificed and blood was collected. At the 168-hour time interval, 3 rats per chemical were sacrificed and blood was collected. The control animals were sacrificed at the 24-hour time interval. Therefore, there were four rats in each of the 4-, 12-, and 24-hour time points for each chemical and four control rats for each chemical. Similarly, there were three rats in the 168-hour time interval for each chemical. The groups for each chemical and time interval are labeled as follows:AP—control—4 rats: blood_AP_0_4, blood_AP_0_5, blood_AP_0_33, and blood_AP_0_34AP—4-hours—4 rats: blood_AP_4_35, blood_AP_4_38, blood_AP_4_39, and blood_AP_4_40AP—12-hours—4 rats: blood_AP_12_41, blood_AP_12_42, blood_AP_12_43, and blood_AP_12_45AP—24-hours—4 rats: blood_AP_24_47, blood_AP_24_48, blood_AP_24_49, and blood_AP_24_51AP—168-hours—3rats: blood_AP_168_53, blood_AP_168_54, and blood_AP_168_56MP—control—4 rats: blood_MP_0_1, blood_MP_0_2, blood_MP_0_3, and blood_MP_0_ 31MP—4-hours—4 rats: blood_MP_4_11, blood_MP_4_12, blood_MP_4_13, and blood_MP_4_22MP—12-hours—4 rats: blood_MP_12_20, blood_MP_12_23, blood_MP_12_24, and blood_MP_12_25MP—24-hours—4 rats: blood_MP_24_6, blood_MP_24_7, blood_MP_24_9, and blood_MP_24_21MP—168-hours—3rats: blood_MP_168_26, blood_MP_168_27, and blood_MP_168_29

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2009-06-01

Last updated: 2008-11-03