Antagonistic effects of methyl-mercury and PCB153 on PC12 cells after a combined and simultaneous exposure

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.