Integration of clinical and gene expression endpoints to explore furan-mediated hepatotoxicity.
Molecular techniques, such as cDNA microarrays, are being used to aid in the elucidation of the mechanisms of toxicity of a variety of compounds. In this study, we evaluate the molecular effects of furan in the rat liver. Sprague-Dawley rats were exposed to 4 or 40 mg/kg furan for up to 14 days. Furan induced an initial degenerative and necrotic phenotype that was followed by inflammation and fibrosis, consistent with previous observations for this compound. RNA was harvested from each lobe of the liver at several time points to observe whether lobe-specific gene expression effects occurred. Similar gene expression changes were observed in all lobes, however the magnitude of gene expression change was more pronounced in the right lobe. Finally, to help determine the correlation between gene expression changes and liver pathology, we applied traditional microarray visualization tools to the assessment of clinical chemistry and pathology parameters.
Hamadeh
Hisham K
HK
National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. hhamadeh@amgen.com
Jayadev
Supriya
S
Gaillard
Elias T
ET
Huang
Qihong
Q
Stoll
Raymond
R
Blanchard
Kerry
K
Chou
Jeff
J
Tucker
Charles J
CJ
Collins
Jennifer
J
Maronpot
Robert
R
Bushel
Pierre
P
Afshari
Cynthia A
CA
D000818:Animals; D018076:DNA, Complementary; D005663:Furans / Q000633:toxicity*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018076:DNA, Complementary; D005663:Furans