Project 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, neurotoxicity 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: APâcontrolâ4 rats: blood_AP_0_4, blood_AP_0_5, blood_AP_0_33, and blood_AP_0_34 APâ4-hoursâ4 rats: blood_AP_4_35, blood_AP_4_38, blood_AP_4_39, and blood_AP_4_40 APâ12-hoursâ4 rats: blood_AP_12_41, blood_AP_12_42, blood_AP_12_43, and blood_AP_12_45 APâ24-hoursâ4 rats: blood_AP_24_47, blood_AP_24_48, blood_AP_24_49, and blood_AP_24_51 APâ168-hoursâ3rats: blood_AP_168_53, blood_AP_168_54, and blood_AP_168_56 MPâcontrolâ4 rats: blood_MP_0_1, blood_MP_0_2, blood_MP_0_3, and blood_MP_0_ 31 MPâ4-hoursâ4 rats: blood_MP_4_11, blood_MP_4_12, blood_MP_4_13, and blood_MP_4_22 MPâ12-hoursâ4 rats: blood_MP_12_20, blood_MP_12_23, blood_MP_12_24, and blood_MP_12_25 MPâ24-hoursâ4 rats: blood_MP_24_6, blood_MP_24_7, blood_MP_24_9, and blood_MP_24_21 MPâ168-hoursâ3rats: blood_MP_168_26, blood_MP_168_27, and blood_MP_168_29
2010-04-08 | E-GEOD-13442 | biostudies-arrayexpress
