title: Gene expression profiles in rat liver treated with perfluorooctanoic acid (PFOA).
abstract: Perfluorooctanoic acid (PFOA; Pentadecafluorooctanoic acid) is widely used in various industrial applications. It is persistent in the environment and does not appear to undergo further degradation or transformation. PFOA is found in tissues including blood of wildlife and humans; however, the environmental fate and biological effects of PFOA remain unclear. Microarray techniques of gene expression have become a powerful approach for exploring the biological effects of chemicals. Here, the Affymetrix, Inc. rat genome 230 2.0 GeneChip was used to identify alterations in gene regulation in Sprague-Dawley rats treated with five different concentrations of PFOA. Male rats were exposed by daily gavage to 1, 3, 5, 10, or 15 mg PFOA/kg, body weight (bw)/day for 21 days and at the end of the exposure, liver was isolated and total liver RNA were used for the gene chip analysis. Over 500 genes, whose expression was significantly (p < 0.0025) altered by PFOA at two-fold changes compared to control, were examined. The effects were dose-dependent with exposure to 10 mg PFOA/kg, bw/day, causing alteration in expression of the greatest number of genes (over 800). Approximately 106 genes and 38 genes were consistently up- or down-regulated, respectively, in all treatment groups. The largest categories of induced genes were those involved in transport and metabolism of lipids, particularly fatty acids. Other induced genes were involved in cell communication, adhesion, growth, apoptosis, hormone regulatory pathways, proteolysis and peptidolysis and signal transduction. The genes expression of which was suppressed were related to transport of lipids, inflammation and immunity, and especially cell adhesion. Several other genes involved in apoptosis; regulation of hormones; metabolism; and G-protein coupled receptor protein signaling pathways were significantly suppressed.
authors.affiliation: Toxico-Biochemistry Section, National Institute of Animal Health, Kannondai 3-1-5, Tsukuba, Ibaraki 305-0856, Japan. guruge@affrc.go.jp
authors.forename: Keerthi S
authors.initials: KS
authors.lastname: Guruge
authors.forename: Leo W Y
authors.initials: LW
authors.lastname: Yeung
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamanaka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Lam
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yamashita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005227:Fatty Acids; D005466:Fluorocarbons; D012333:RNA, Messenger; C023036:perfluorooctanoic acid