title: Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R.
abstract: Polychlorinated biphenyls (PCB), synthetic, persistent organic pollutants (POP), are detected ubiquitously, in water, soil, air, and sediments, as well as in animals and humans. PCB are associated with range of adverse health effects, such as interference with the immune system and nervous system, reproductive abnormalities, fetotoxicity, carcinogenicity, and endocrine disruption. Our objective was to determine the effects of three structurally different PCB congeners, PCB118, PCB 126, and PCB 153, each at two concentrations, on the steroidogenic capacity and proteome of human adrenocortical carcinoma cell line cultures (H295R) . After 48 h of exposure, cell viability was monitored and estradiol, testosterone, cortisol and progesterone secretion measured to quantify steroidogenic capacity of the cells. Two-dimensional (2D) gel-based proteomics was used to screen for proteome alterations in H295R cells in response to the PCB. Exposure to PCB 118 increased estradiol and cortisol secretion, while exposure to PCB 153 elevated estradiol secretion. PCB 126 was the most potent congener, increasing estradiol, cortisol, and progesterone secretion in exposed H295R cells. Seventy-three of the 711 spots analyzed showed a significant difference in normalized spot volumes between controls (vehicle only) and at least one exposure group. Fourteen of these protein spots were identified by liquid chromatography with mass spectroscopy (LC-MS/MS). Exposure to three PCB congeners with different chemical structure perturbed steroidogenesis and protein expression in the H295R in vitro model. This study represents an initial analysis of the effects on proteins and hormones in the H295R cell model, and additional studies are required in order to obtain a more complete understanding of the pathways disturbed by PCB congeners in H295R cells. Overall, alterations in protein regulation and steroid hormone synthesis suggest that exposure to PCB disturbs several cellular processes, including protein synthesis, stress response, and apoptosis.
authors.affiliation: a Department of Production Animal Sciences , Norwegian School Veterinary Science , Oslo.
authors.forename: Nina Hårdnes
authors.initials: NH
authors.lastname: Tremoen
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fowler
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.forename: Steven
authors.initials: S
authors.lastname: Verhaegen
authors.forename: Anette
authors.initials: A
authors.lastname: Krogenæs
mesh_terms: D018268:Adrenocortical Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D052244:Endocrine Disruptors / Q000633:toxicity; D004958:Estradiol / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011374:Progesterone / Q000096:biosynthesis; D020543:Proteome / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D052244:Endocrine Disruptors; D020543:Proteome; D013256:Steroids; C070055:2,3',4,4',5-pentachlorobiphenyl; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; D006854:Hydrocortisone; C014024:2,4,5,2',4',5'-hexachlorobiphenyl