PMID- 11343254
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20240109
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 33
IP  - 5
DP  - 2001 May
TI  - RNA expression in the early characterization of hepatotoxicants in Wistar rats by 
      high-density DNA microarrays.
PG  - 1239-58
AB  - High-density microarrays are useful tools to study gene expression for the 
      purpose of characterizing functional tissue changes in response to the action of 
      drugs and chemicals. To test whether high-density expression data can identify 
      mechanisms of toxicity and to identify an unknown sample through its RNA 
      expression pattern, groups of male Wistar rats were administered 6 
      hepatotoxicants. The compounds chosen for this study were microcystin-LR (MLR), 
      phenobarbital (PB), lipopolysaccharide (LPS), carbon tetrachloride (CT), 
      thioacetamide (THA), and cyproterone acetate (CPA). These hepatotoxicants are 
      known to induce adverse liver effects through different mechanisms. Liver mRNA 
      was isolated and used to generate biotinylated cRNA for hybridization to a custom 
      1,600-rat gene DNA microarray. Treatment correlation matrices analyzed 
      hybridization data from a hepatotoxicant-blinded sample, with gene expression 
      coefficients (GEC) evaluated by means of hierarchical cluster analysis and visual 
      representation as dendrograms. The experimental liver toxicity from the different 
      treatments was confirmed by means of concurrent histopathology, liver enzymes, 
      and bilirubin assays. This toxico genomic analysis identified multiple genes and 
      groups of genes that were affected by the hepatotoxicants on study, indicating 
      that high-density microarray expression data are useful to identify groups of 
      genes involved in toxicity. In addition, the mRNA expression profile of an 
      unidentified sample can be accurately identified when compared with the 
      expression profiles resident in the data set. This study supports the use of gene 
      expression-profiling technology to determine or to predict toxic liver effects.
FAU - Bulera, S J
AU  - Bulera SJ
AD  - Drug Safety Evaluation and Molecular Biology, Pfizer Global Research and 
      Development, Ann Arbor, MI 48105, USA. steven.bulera@pfizer.com
FAU - Eddy, S M
AU  - Eddy SM
FAU - Ferguson, E
AU  - Ferguson E
FAU - Jatkoe, T A
AU  - Jatkoe TA
FAU - Reindel, J F
AU  - Reindel JF
FAU - Bleavins, M R
AU  - Bleavins MR
FAU - De La Iglesia, F A
AU  - De La Iglesia FA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Poisons)
RN  - 63231-63-0 (RNA)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Animals
MH  - Bilirubin/metabolism
MH  - Cluster Analysis
MH  - Gene Expression/drug effects
MH  - Liver/*drug effects/enzymology/*metabolism/pathology
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - Poisons/*pharmacology
MH  - RNA/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Single-Blind Method
EDAT- 2001/05/09 10:00
MHDA- 2001/06/02 10:01
CRDT- 2001/05/09 10:00
PHST- 2001/05/09 10:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2001/05/09 10:00 [entrez]
AID - S0270-9139(01)43050-3 [pii]
AID - 10.1053/jhep.2001.23560 [doi]
PST - ppublish
SO  - Hepatology. 2001 May;33(5):1239-58. doi: 10.1053/jhep.2001.23560.