Document Detail

Promotion of hepatocarcinogenesis by perfluoroalkyl acids in rainbow trout.
MedLine Citation:
PMID:  21984479     Owner:  NLM     Status:  MEDLINE    
Previously, we reported that perfluorooctanoic acid (PFOA) promotes liver cancer in a manner similar to that of 17β-estradiol (E2) in rainbow trout. Also, other perfluoroalkyl acids (PFAAs) are weakly estrogenic in trout and bind the trout liver estrogen receptor. The primary objective of this study was to determine whether multiple PFAAs enhance hepatic tumorigenesis in trout, an animal model that represents human insensitivity to peroxisome proliferation. A two-stage chemical carcinogenesis model was employed in trout to evaluate PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and 8:2 fluorotelomer alcohol (8:2FtOH) as complete carcinogens or promoters of aflatoxin B(1) (AFB(1))- and/or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced liver cancer. A custom trout DNA microarray was used to assess hepatic transcriptional response to these dietary treatments in comparison with E2 and the classic peroxisome proliferator, clofibrate (CLOF). Incidence, multiplicity, and size of liver tumors in trout fed diets containing E2, PFOA, PFNA, and PFDA were significantly higher compared with AFB(1)-initiated animals fed control diet, whereas PFOS caused a minor increase in liver tumor incidence. E2 and PFOA also enhanced MNNG-initiated hepatocarcinogenesis. Pearson correlation analyses, unsupervised hierarchical clustering, and principal components analyses showed that the hepatic gene expression profiles for E2 and PFOA, PFNA, PFDA, and PFOS were overall highly similar, though distinct patterns of gene expression were evident for each treatment, particularly for PFNA. Overall, these data suggest that multiple PFAAs can promote liver cancer and that the mechanism of promotion may be similar to that of E2.
Abby D Benninghoff; Gayle A Orner; Clarissa H Buchner; Jerry D Hendricks; Aaron M Duffy; David E Williams
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-09
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  125     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-22     Completed Date:  2012-06-06     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  69-78     Citation Subset:  IM    
Department of Animal, Dairy and Veterinary Sciences and Graduate Program in Toxicology, Utah State University, Logan, Utah 84322, USA.
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MeSH Terms
Aflatoxin B1 / toxicity
Alkanesulfonic Acids / toxicity
Caprylates / toxicity
Carcinogenicity Tests
Decanoic Acids / toxicity
Endocrine Disruptors / chemistry,  toxicity*
Fluorocarbons / chemistry,  toxicity*
Gene Expression / drug effects*
Gene Expression Profiling
Hydrocarbons, Fluorinated / toxicity
Liver Neoplasms, Experimental / chemically induced*,  genetics,  pathology
Methylnitronitrosoguanidine / toxicity
Oligonucleotide Array Sequence Analysis
Oncorhynchus mykiss*
Real-Time Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/8-2 fluorotelomer alcohol; 0/Alkanesulfonic Acids; 0/Caprylates; 0/Decanoic Acids; 0/Endocrine Disruptors; 0/Fluorocarbons; 0/Hydrocarbons, Fluorinated; 1162-65-8/Aflatoxin B1; 1763-23-1/perfluorooctane sulfonic acid; 335-67-1/perfluorooctanoic acid; 335-76-2/perfluorodecanoic acid; 70-25-7/Methylnitronitrosoguanidine; 76-21-1/hexadecafluoro-nonanoic acid

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