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| Status |
Public on Mar 15, 2012 |
| Title |
Discover preclinical biomarkers of hepatotoxicity: Acetaminophen and Carbon tetrachloride |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Preclinical biomarkers useful for identification of idiosyncratic drugs have not been identified. It is hypothesized that patterns of transcript expression for the hepatotoxicants, including classical and idiosyncratic hepatotoxicants, are similar and the patterns differ from those of non-hepatotoxicants. This experiment is part of the biomarkers study, and focus on two clasical hepatotoxicants: Acetaminophen and Carbon tetrachloride. We have employed whole genome microarray expression profiling to identify liver gene expression changes induced by hepatotoxicants. For the same animal, urinary microRNA profiling were analyzed. APAP and CCl4 both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl4. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. From the same animals, liver gene expression profiling was performed using whole genome microarrays. Eight putative target genes were found to be significantly altered in the liver of APAP and CCl4 treated animals.
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| Overall design |
Acetaminophen induced liver gene expression changes in rats (Six to seven week-old male Sprague-Dawley rats, provided by the US Food and Drug Administration National Center for Toxicological Research (NCTR) breeding colonies, were used for the study.) were measured at 6 hours, 24 hours, 3 days and 7 days after exposure to doses of 0, 100 and 1250 mg/kg. Carbon tetrachloride induced liver gene expression changes in rats were measured at 6 hours, 24 hours and 3 days after exposure to doses of 0, 50 and 2000 mg/kg. Each group has at least 4 animals, total of 96 samples.
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| Contributor(s) |
Xi Y |
| Citation(s) |
22112502 |
| Submission date |
Oct 11, 2011 |
| Last update date |
Dec 21, 2016 |
| Contact name |
Zhenqiang Su |
| E-mail(s) |
zhenqiangsu@gmail.com
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| Phone |
501-584-8331
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| Organization name |
Thomson Reuters
|
| Department |
IP & Science
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| Street address |
22 Thomson Place
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02210 |
| Country |
USA |
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| Platforms (1) |
| GPL4135 |
Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Feature Number version) |
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| Samples (96)
|
| GSM813941 |
A04, Liver, control, 6h Cntl_6h_1 |
| GSM813942 |
A05, Liver, APAP, 100mg/kg, 6h APAP100_6h_2 |
| GSM813943 |
A06, Liver, APAP, 100mg/kg, 6h APAP100_6h_2 |
| GSM813944 |
A07, Liver, APAP, 100mg/kg, 6h APAP100_6h_2 |
| GSM813945 |
A08, Liver, APAP, 100mg/kg, 6h APAP100_6h_2 |
| GSM813946 |
A09, Liver, APAP, 100mg/kg, 6h APAP100_6h_2 |
| GSM813947 |
A10, Liver, APAP, 1250mg/kg, 6h APAP1250_6h_3 |
| GSM813948 |
A11, Liver, APAP, 1250mg/kg, 6h APAP1250_6h_3 |
| GSM813949 |
A12, Liver, APAP, 1250mg/kg, 6h APAP1250_6h_3 |
| GSM813950 |
A13, Liver, APAP, 1250mg/kg, 6h APAP1250_6h_3 |
| GSM813951 |
A14, Liver, APAP, 1250mg/kg, 6h APAP1250_6h_3 |
| GSM813952 |
A15, Liver, control, 24h Cntl_24h_4 |
| GSM813953 |
A16, Liver, control, 24h Cntl_24h_4 |
| GSM813954 |
A17, Liver, control, 24h Cntl_24h_4 |
| GSM813955 |
A18, Liver, control, 24h Cntl_24h_4 |
| GSM813956 |
A19, Liver, APAP, 100mg/kg, 24h APAP100_24h_5 |
| GSM813957 |
A20, Liver, APAP, 100mg/kg, 24h APAP100_24h_5 |
| GSM813958 |
A21, Liver, APAP, 100mg/kg, 24h APAP100_24h_5 |
| GSM813959 |
A22, Liver, APAP, 100mg/kg, 24h APAP100_24h_5 |
| GSM813960 |
A23, Liver, APAP, 100mg/kg, 24h APAP100_24h_5 |
| GSM813961 |
A24, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813962 |
A25, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813963 |
A26, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813964 |
A27, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813965 |
A28, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813966 |
A29, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813967 |
A30, Liver, APAP, 1250mg/kg, 24h APAP1250_24h_6 |
| GSM813968 |
A31, Liver, control, 3d Cntl_3d_7 |
| GSM813969 |
A32, Liver, control, 3d Cntl_3d_7 |
| GSM813970 |
A33, Liver, control, 3d Cntl_3d_7 |
| GSM813971 |
A34, Liver, control, 3d Cntl_3d_7 |
| GSM813972 |
A35, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813973 |
A36, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813974 |
A37, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813975 |
A38, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813976 |
A39, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813977 |
A40, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813978 |
A41, Liver, APAP, 1250mg/kg, 3d APAP1250_3d_8 |
| GSM813979 |
A42, Liver, control, 7d Cntl_7d_9 |
| GSM813980 |
A43, Liver, control, 7d Cntl_7d_9 |
| GSM813981 |
A44, Liver, control, 7d Cntl_7d_9 |
| GSM813982 |
A45, Liver, control, 7d Cntl_7d_9 |
| GSM813983 |
A46, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813984 |
A47, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813985 |
A48, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813986 |
A49, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813987 |
A50, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813988 |
A51, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813989 |
A52, Liver, APAP, 1250mg/kg, 7d APAP1250_7d_10 |
| GSM813990 |
B01, Liver, control, 6h Cntl_6h_1 |
| GSM813991 |
B02, Liver, control, 6h Cntl_6h_1 |
| GSM813992 |
B03, Liver, control, 6h Cntl_6h_1 |
| GSM813993 |
B04, Liver, control, 6h Cntl_6h_1 |
| GSM813994 |
B06, Liver, CCl4, 50mg/kg, 6h CCl50_6h_2 |
| GSM813995 |
B07, Liver, CCl4, 50mg/kg, 6h CCl50_6h_2 |
| GSM813996 |
B08, Liver, CCl4, 50mg/kg, 6h CCl50_6h_2 |
| GSM813997 |
B09, Liver, CCl4, 50mg/kg, 6h CCl50_6h_2 |
| GSM813998 |
B10, Liver, CCl4, 50mg/kg, 6h CCl50_6h_2 |
| GSM813999 |
B11, Liver, CCl4, 2000mg/kg, 6h CCl2000_6h_3 |
| GSM814000 |
B12, Liver, CCl4, 2000mg/kg, 6h CCl2000_6h_3 |
| GSM814001 |
B13, Liver, CCl4, 2000mg/kg, 6h CCl2000_6h_3 |
| GSM814002 |
B14, Liver, CCl4, 2000mg/kg, 6h CCl2000_6h_3 |
| GSM814003 |
B15, Liver, CCl4, 2000mg/kg, 6h CCl2000_6h_3 |
| GSM814004 |
B16, Liver, control, 24h Cntl_24h_4 |
| GSM814005 |
B17, Liver, control, 24h Cntl_24h_4 |
| GSM814006 |
B18, Liver, control, 24h Cntl_24h_4 |
| GSM814007 |
B19, Liver, control, 24h Cntl_24h_4 |
| GSM814008 |
B20, Liver, control, 24h Cntl_24h_4 |
| GSM814009 |
B21, Liver, CCl4, 50mg/kg, 24h CCl50_24h_5 |
| GSM814010 |
B22, Liver, CCl4, 50mg/kg, 24h CCl50_24h_5 |
| GSM814011 |
B23, Liver, CCl4, 50mg/kg, 24h CCl50_24h_5 |
| GSM814012 |
B24, Liver, CCl4, 50mg/kg, 24h CCl50_24h_5 |
| GSM814013 |
B25, Liver, CCl4, 50mg/kg, 24h CCl50_24h_5 |
| GSM814014 |
B26, Liver, CCl4, 2000mg/kg, 24h CCl2000_24h_6 |
| GSM814015 |
B27, Liver, CCl4, 2000mg/kg, 24h CCl2000_24h_6 |
| GSM814016 |
B28, Liver, CCl4, 2000mg/kg, 24h CCl2000_24h_6 |
| GSM814017 |
B29, Liver, CCl4, 2000mg/kg, 24h CCl2000_24h_6 |
| GSM814018 |
B30, Liver, CCl4, 2000mg/kg, 24h CCl2000_24h_6 |
| GSM814019 |
B31, Liver, control, 3d Cntl_3d_7 |
| GSM814020 |
B32, Liver, control, 3d Cntl_3d_7 |
| GSM814021 |
B33, Liver, control, 3d Cntl_3d_7 |
| GSM814022 |
B34, Liver, control, 3d Cntl_3d_7 |
| GSM814023 |
B35, Liver, control, 3d Cntl_3d_7 |
| GSM814024 |
B36, Liver, CCl4, 50mg/kg, 3d CCl50_3d_8 |
| GSM814025 |
B37, Liver, CCl4, 50mg/kg, 3d CCl50_3d_8 |
| GSM814026 |
B38, Liver, CCl4, 50mg/kg, 3d CCl50_3d_8 |
| GSM814027 |
B39, Liver, CCl4, 50mg/kg, 3d CCl50_3d_8 |
| GSM814028 |
B40, Liver, CCl4, 50mg/kg, 3d CCl50_3d_8 |
| GSM814029 |
B41, Liver, CCl4, 2000mg/kg, 3d CCl2000_3d_9 |
| GSM814030 |
B42, Liver, CCl4, 2000mg/kg, 3d CCl2000_3d_9 |
| GSM814031 |
B43, Liver, CCl4, 2000mg/kg, 3d CCl2000_3d_9 |
| GSM814032 |
B44, Liver, CCl4, 2000mg/kg, 3d CCl2000_3d_9 |
| GSM814033 |
B45, Liver, CCl4, 2000mg/kg, 3d CCl2000_3d_9 |
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| Relations |
| BioProject |
PRJNA146629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32891_RAW.tar |
739.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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