Title: Transcript profiles of PFAAs in trout liver

Accession Number: GSE31085

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31085

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Oncorhynchus mykiss

Summary: Background: 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). Objectives: 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 proliferators. Methods: 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 B1 (AFB1)- 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). Results: Incidence, multiplicity and size of liver tumors in trout fed diets containing E2, PFOA, PFNA and PFDA were significantly higher compared to AFB1-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. Conclusions: Overall, these data suggest that multiple PFAAs can promote liver cancer and that the mechanism of promotion may be similar to that for E2.

Publication(s) associated with this dataset:

• Benninghoff AD, Orner GA, Buchner CH, Hendricks JD, Duffy AM, Williams DE. 2012. Promotion of hepatocarcinogenesis by perfluoroalkyl acids in rainbow trout. Toxicol Sci 125(1):69-78. doi:10.1093/toxsci/kfr267 PMID:21984479 PMCID:PMC3243748