title: Perfluorinated compounds differentially affect steroidogenesis and viability in the human adrenocortical carcinoma (H295R) in vitro cell assay.
abstract: Perfluorinated compounds (PFCs) comprise a large class of man-made chemicals of which some are persistent and present throughout the ecosystem. This raises concerns about potential harmful effects of such PFCs on humans and the environment. In order to investigate the effects of potentially harmful PFCs on steroid hormone production, human adrenocortical H295R cells were exposed to three persistent PFCs including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) at six different concentrations (6nM to 600μM) for 48h. Exposure to 600μM PFOS resulted in a dose-responsive increase in oestradiol as well as a smaller dose-responsive increase in progesterone and testosterone secretion measured using radioimmunoassay. The aromatase activity was not significantly altered by PFOS. Only small changes in hormone secretion were detected following exposure to PFOA and PFNA. Gene expression of CYP11A, quantified using qRT-PCR was decreased by all exposure doses of PFOA, whereas HMGR expression was decreased by 60nM PFNA. The viability markedly decreased by exposure to 600μM of PFOA or PFNA, but not PFOS. Flow cytometric analysis demonstrated a significant increase in apoptosis following exposure to PFNA at the highest concentration. We conclude that PFOS is capable of altering steroidogenesis in the H295R in vitro model by a mechanism other than changes in gene expression or activity of aromatase. Additionally, PFCs appear to differentially affect cell viability with induction of cell death via apoptosis at high doses of PFNA.
authors.affiliation: Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway. Marianne.Kraugerud@nvh.no
authors.forename: Marianne
authors.initials: M
authors.lastname: Kraugerud
authors.forename: Karin E
authors.initials: KE
authors.lastname: Zimmer
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.forename: Steven
authors.initials: S
authors.lastname: Verhaegen
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017738:Alkanesulfonic Acids / Q000633:toxicity; D001141:Aromatase / Q000378:metabolism; D002210:Caprylates / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D011419:Propidium; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; D012334:RNA, Neoplasm; D013256:Steroids; D005576:Colforsin; D011419:Propidium; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme