| Promotion of Hepatocarcinogenesis by Perfluoroalkyl Acids in Rainbow Trout. | |
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MedLine Citation:
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PMID: 21984479 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Previously, we reported that perfluorooctanoic acid (PFOA) promotes liver cancer in 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 (ER). 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 to 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 to 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 for E2. |
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Authors:
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Abby D Benninghoff; Gayle A Orner; Clarissa H Buchner; Jerry D Hendricks; Aaron M Duffy; David E Williams |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-9 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: - ISSN: 1096-0929 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Animal, Dairy and Veterinary Sciences and the Graduate Program in Toxicology, Utah State University, 4815 Old Main Hill, Logan, UT, 84322, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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