title: Antagonistic effects of methyl-mercury and PCB153 on PC12 cells after a combined and simultaneous exposure.
abstract: The study of interactions for those substances which tend to accumulate in food and affect the nervous system appears to be a fundamental point to characterize the combined exposure in vitro. In this study we included two food contaminants which are known neurotoxicants: methyl-mercury (Me-Hg) and the ortho-substituted PCB 153. PC12 cells were treated with Me-Hg (range 1e-7, 2e-6 M) and PCB153 (range 1e-5, 4e-4 M) in single and combined synchronous experiments and a mathematical model was set up according to the Loewe additivity criterion to evaluate the level of interaction between toxicants, using viability as end-point. At some concentrations (Me-Hg 5e-7 M and PCB153 1e-4 and 2e-4 M; Me-Hg 1e-6M and PCB153 5e-5 M; Me-Hg 1e-7 M and PCB153 4e-4 M), a statistically significant antagonist effect was observed. No interaction was observed for other combinations. The analysis of other toxicological parameters known to be modified in single exposure experiments (TBARS and intra-cellular dopamine) confirmed the viability results. The results of our work represent a starting point to generate novel information on the interactions between PCB153 and Me-Hg in vitro, as well as a new relevant experimental and mathematical approach useful to investigate the effects of different toxicant mixtures.
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Vettori
authors.forename: M
authors.initials: M
authors.lastname: Goldoni
authors.forename: A
authors.initials: A
authors.lastname: Caglieri
authors.forename: D
authors.initials: D
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Folesani
authors.forename: S
authors.initials: S
authors.lastname: Ceccatelli
authors.forename: A
authors.initials: A
authors.lastname: Mutti
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D004785:Environmental Pollutants / Q000633:toxicity; D005506:Food Contamination; D005562:Formazans / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004785:Environmental Pollutants; D005562:Formazans; D008767:Methylmercury Compounds; D013778:Tetrazolium Salts; D013858:Thiobarbiturates; C079782:MTT formazan; D011078:Polychlorinated Biphenyls; C020771:methylmercury hydroxide; C029684:thiobarbituric acid; D004298:Dopamine