Methylmercury at low doses modulates the toxicity of PCB153 on PC12 neuronal cell line in asynchronous combination experiments

• Published in: Food and chemical toxicology Vol. 46; no. 2; pp. 808 - 811
• Main Authors: Goldoni, M., Caglieri, A., Poli, D., Vettori, M.V., Ceccatelli, S., Mutti, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-02-2008; New York, NY Elsevier Science
• Subjects: animal models; Animals; antagonists; Biological and medical sciences; cell lines; Cell Survival; Chemical and industrial products toxicology. Toxic occupational diseases; Combined exposure; dosage; Dose-Response Relationship, Drug; Drug Antagonism; Drug Combinations; Food Contamination; in vitro studies; Medical sciences; Medicin och hälsovetenskap; Metals and various inorganic compounds; methylmercury compounds; Methylmercury Compounds - administration & dosage; Methylmercury Compounds - toxicity; Methyl–Mercury; neurons; Neurotoxicity; neurotoxins; PC12; PC12 Cells - drug effects; PC12 Cells - metabolism; PCB153; polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Rats; Toxicology; viability; PC12; SD; PCB153; Neurotoxicity; Combined exposure; DMSO; Me–Hg; Methyl–Mercury; MTT; PCB; Drug combination; Asynchronous; Nervous system diseases; Methyl-Mercury; Toxicity; Low dose; Nervous system; In vitro; Toxic association; Heavy metal; Cell line; Neuron; Established cell line; Mercury Organic compounds
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2007.09.104

Me–Hg and PCB153 are known neurotoxic contaminants which tend to accumulate in food, particularly in fish. Aim of this study was to perform asynchronous and combined exposure to Me–Hg and PCB153 in a neuronal rat cell line (PC12) to better characterise the antagonism observed at some combination concentrations.
PC12 cells were treated with three concentrations of Me–Hg (0.1–0.5–1.0
μM) and PCB153 at one concentration (175
μM) in single and combined asynchronous exposures, using viability (MTT assay) as end-point.
At all concentrations used, a statistically significant antagonistic effect was observed when Me–Hg preceded PCB153 exposure, while effect was additive when PCB153 preceded Me–Hg exposure. The antagonism is particularly evident at low concentrations of Me–Hg (0.1
μM).
In conclusion, combined asynchronous exposure showed that whereas Me–Hg can modulate PCB153 toxicity, the opposite seems not to be true. Therefore, the use of asynchronous exposure could be a promising approach to study the mechanisms of toxicity of binary mixtures.