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Vol. 297, Issue 3, 895-905, June 2001
Department of Molecular Biosciences, School of Veterinary Medicine,
University of California, Davis, California (M.J.B., A.B.); and
Molecular Dynamics, Sunnyvale, California (D.J., S.P., J.E.)
DNA arrays containing 260 unique genes involved in phase I and II
metabolism, heat shock, DNA repair, inflammation, transcription, and
housekeeping were used to examine gene expression patterns in liver and
kidney in response to five classes of chemicals (polyaromatic hydrocarbons: benzo(a)pyrene, 3-methylcholanthrene; DNA
alkylators: dimethylnitrosamine, ethylnitrosourea; peroxisome
proliferators: diethylhexylphthalate, clofibrate; heavy metals:
CdCl2, HgCl2; and oxidative stressors:
CCl4, bromobenzene). Time course experiments in
mice were carried out in both tissues for each chemical and dose-response studies were used to further evaluate several of these
chemicals. Each pair of chemicals yielded a similar pattern of gene
expression distinct from the other four classes of chemicals. Both
peroxisome proliferators up-regulated Cyp4a10, acyl-CoA thioesterase, and insulin-like growth factor binding protein-1, whereas the DNA
alkylators altered the expression of monokine induced by
-interferon, the metallothioneins, p21, and several acute phase
proteins. For each of the five classes of chemicals tested, several
genes that were induced or repressed were common in each chemical
exposure, whereas other genes were unique for that specific class of
compound. Both time and dose are important factors in differentiating
between chemical classes. Likewise, comparison of changes in messenger RNA expression between the kidney and liver of treated animals indicates that gene arrays may be useful in determining the comparative toxicity of chemicals in various tissues but that exposure to uncharacterized chemicals will have to be monitored in several tissues.
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