Genomic profiling reveals an alternate mechanism for hepatic tumor promotion by perfluorooctanoic acid in rainbow trout.

Environmental Health Perspectives
Susan C TiltonDavid E Williams

Abstract

Perfluorooctanoic acid (PFOA) is a potent hepatocarcinogen and peroxisome proliferator (PP) in rodents. Humans are not susceptible to peroxisome proliferation and are considered refractory to carcinogenesis by PPs. Previous studies with rainbow trout indicate they are also insensitive to peroxisome proliferation by the PP dehydroepiandrosterone (DHEA), but are still susceptible to enhanced hepatocarcinogenesis after chronic exposure. In this study, we used trout as a unique in vivo tumor model to study the potential for PFOA carcinogenesis in the absence of peroxisome proliferation compared with the structurally diverse PPs clofibrate (CLOF) and DHEA. Mechanisms of carcinogenesis were identified from hepatic gene expression profiles phenotypically anchored to tumor outcome. We fed aflatoxin B(1) or sham-initiated animals 200-1,800 ppm PFOA in the diet for 30 weeks for tumor analysis. We subsequently examined gene expression by cDNA array in animals fed PFOA, DHEA, CLOF, or 5 ppm 17beta-estradiol (E(2), a known tumor promoter) in the diet for 14 days. PFOA (1,800 ppm or 50 mg/kg/day) and DHEA treatments resulted in enhanced liver tumor incidence and multiplicity (p < 0.0001), whereas CLOF showed no effect. Carcinogenesis was ind...Continue Reading

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Citations

Dec 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Abby D BenninghoffDavid E Williams
Oct 11, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Abby D BenninghoffDavid E Williams
Jun 28, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Silvia BijlandHans M G Princen
Jul 26, 2012·Environmental Science and Pollution Research International·N JacquetP Vasseur
Jun 15, 2013·Environmental Science and Pollution Research International·Lisbeth Stigaard Kjeldsen, Eva Cecilie Bonefeld-Jørgensen
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Jan 13, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·David E WilliamsGeorge S Bailey
Nov 6, 2014·Critical Reviews in Toxicology·Cathrine Carlsen BachTine Brink Henriksen
Apr 25, 2016·Environmental Science and Pollution Research International·Luisa GiariGiuseppe Castaldelli
Apr 25, 2014·Marine Pollution Bulletin·Jae-Sung Rhee, Jae-Seong Lee
Jun 9, 2016·Critical Reviews in Toxicology·Cathrine Carlsen BachGunnar Toft
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Nov 7, 2017·Environmental Toxicology and Chemistry·John Charles RotondoFernanda Martini
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Nov 5, 2020·International Journal of Environmental Research and Public Health·Marco BonatoGianfranco Santovito
Mar 22, 2014·Chemical Research in Toxicology·Sergio ManzettiDavid van der Spoel

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
enzyme
PCR
two-hybrid

Software Mentioned

GraphPad Prism
Cytel
StatXact
LOWESS
SAS
GeneSpring

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