Gene expression analysis reveals chemical-specific profiles.
The application of gene expression profiling technology to examine multiple genes and signaling pathways simultaneously promises a significant advance in understanding toxic mechanisms to ultimately aid in protection of public health. Public and private efforts in the new field of toxicogenomics are focused on populating databases with gene expression profiles of compounds where toxicological and pathological endpoints are well characterized. The validity and utility of a toxicogenomics is dependent on whether gene expression profiles that correspond to different chemicals can be distinguished. The principal hypothesis underlying a toxicogenomic or pharmacogenomic strategy is that chemical-specific patterns of altered gene expression will be revealed using high-density microarray analysis of tissues from exposed organisms. Analyses of these patterns should allow classification of toxicants and provide important mechanistic insights. This report provides a verification of this hypothesis. Patterns of gene expression corresponding to liver tissue derived from chemically exposed rats revealed similarity in gene expression profiles between animals treated with different agents from a common class of compounds, peroxisome proliferators [clofibrate (ethyl-p-chlorophenoxyisobutyrate), Wyeth 14,643 ([4-chloro-6(2,3-xylidino)-2-pyrimidinylthio]acetic acid), and gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid)], but a very distinct gene expression profile was produced using a compound from another class, enzyme inducers (phenobarbital).
Hamadeh
Hisham K
HK
National Institute of Environmental Health Sciences, P.O. Box 12233, MD2-04, Research Triangle Park, NC 27709, USA.
Bushel
Pierre R
PR
Jayadev
Supriya
S
Martin
Karla
K
DiSorbo
Olimpia
O
Sieber
Stella
S
Bennett
Lee
L
Tennant
Raymond
R
Stoll
Raymond
R
Barrett
J Carl
JC
Blanchard
Kerry
K
Paules
Richard S
RS
Afshari
Cynthia A
CA
D000818:Animals; D002994:Clofibrate / Q000737:chemistry / Q000633:toxicity; D019295:Computational Biology; D018076:DNA, Complementary / Q000032:analysis; D015248:Gemfibrozil / Q000737:chemistry / Q000633:toxicity; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000145:classification / Q000379:methods*; D023281:Genomics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010363:Pattern Recognition, Automated; D020025:Peroxisome Proliferators / Q000737:chemistry / Q000633:toxicity*; D010634:Phenobarbital / Q000737:chemistry / Q000633:toxicity*; D011743:Pyrimidines / Q000737:chemistry / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship
D018076:DNA, Complementary; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; C006253:pirinixic acid; D002994:Clofibrate; D015248:Gemfibrozil; D010634:Phenobarbital