title: Integration of clinical and gene expression endpoints to explore furan-mediated hepatotoxicity.
abstract: 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.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. hhamadeh@amgen.com
authors.forename: Hisham K
authors.initials: HK
authors.lastname: Hamadeh
authors.forename: Supriya
authors.initials: S
authors.lastname: Jayadev
authors.forename: Elias T
authors.initials: ET
authors.lastname: Gaillard
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.forename: Raymond
authors.initials: R
authors.lastname: Stoll
authors.forename: Kerry
authors.initials: K
authors.lastname: Blanchard
authors.forename: Jeff
authors.initials: J
authors.lastname: Chou
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Tucker
authors.forename: Jennifer
authors.initials: J
authors.lastname: Collins
authors.forename: Robert
authors.initials: R
authors.lastname: Maronpot
authors.forename: Pierre
authors.initials: P
authors.lastname: Bushel
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Afshari
mesh_terms: 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
chemical_list: D018076:DNA, Complementary; D005663:Furans