Submitted on September 28, 2007
Accepted on June 5, 2008
Comparative hepatic gene expression profiling of rats treated with 1H,1H,2H,2H-heptadecafluorodecan-1-ol or with pentadecafluorooctanoic acid
Anja Julie Nilsen1, Maria A. Landin1, Kristin H. Haug2, Frode Fonnum3, Urs Berger4, and Harald Osmundsen1*
1 Oral biology, University of Oslo, Oslo, Norway
2 Medical biochemistry, University of Oslo, Oslo, Norway
3 Medical biochemistry, Univeristy of Oslo, Oslo, Norway
4 Polar Environment, Norwegian Institute of Air Research, Tromsoe, Norway
* To whom correspondence should be addressed. E-mail: haraldo{at}odont.uio.no.
Pentadecafluorooctanoic acid is an established peroxisome proliferator. Little is known about effects of treatment with 1H, 1H, 2H, 2H-heptadecafluorodecan-1-ol, which is metabolised to pentadecafluorooctanoic acid. We have compared effects of various dosages (3, 10 or 25mg/kg body-wt) of each of these compounds on hepatic gene-expression in rats using microarrays. Microarray data were validated by real-time RT-PCR. Expression data were also correlated with hepatic activities of selected enzymes, and with hepatic levels of pentadecafluorooctanoic acid and 1H, 1H, 2H, 2H-heptadecafluoro-decan-1-ol.
Pentadecafluorooctanoic acid caused the more powerful change in gene expression, both in terms of number of genes affected and extents of change in expression. Across the dosages used pentadecafluorooctanoic acid or 1H, 1H, 2H, 2H-heptadecafluorodecan-1-ol caused significant (P
0.05) changes in expression for 441 and 105 genes, respectively. With 1H, 1H, 2H, 2H-heptadecafluorodecan-1-ol about 38% of the 105 genes exhibited decreased expression with a dose of 25mg/kg body-wt, these genes also appearing less responsive to treatment at the lower dosages. Bioinformatic analysis suggested these genes to be associated with regulatory functions. With pentadecafluorooctanoic acid increasing dosage up to 10mg/kg body-wt. brought about progressive increase in expression of affected genes. Pathways analysis suggested similar effects of the two compounds on lipid and amino acid metabolism. Marked differences were also found, particularly with respect to effects on genes related to oxidative phosphorylation, oxidative metabolism, free radical scavenging, xenobiotic metabolism, and complement and coagulation cascades.
