An in vitro approach to assess the toxicity of certain food contaminants: methylmercury and polychlorinated biphenyls.
Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are widespread environmental pollutants and food contaminants, and known developmental neurotoxicants. Aim of this study was to evaluate the effects of MeHg, PCB 126 and PCB 153 in a battery of in vitro cell systems. A total of 17 cell types were utilized, including nervous system (neuronal and astroglial) and non-nervous system cells. End-points measured included MTT reduction, Trypan blue exclusion and (3)H-thymidine incorporation into DNA. Results indicate that this approach would identify these three compounds as neurotoxicants, and would also point out to the thyroid (for PCB 126 and MeHg) and the prostate (for both PCBs) as important additional targets. Tests of binary combinations of MeHg and PCBs indicated no interaction and an additive response, in agreement with other recent reports. Cerebellar granule neurons from mice with genetically determined low glutathione levels were more sensitive than wild-type neurons to the toxicity of all three compounds, supporting a role for oxidative stress in their neurotoxicity. These findings provide initial evidence that a relatively rapid in vitro screening approach can be developed, that would provide initial information useful for assessing neurotoxicity, as well as indication on potential other targets of biological action or toxicity.
Costa
Lucio G
LG
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Department of Human Anatomy, Pharmacology and Forensic Sciences, University of Parma Medical School, Parma, Italy. Electronic address: lgcosta@u.washington.edu.
Fattori
Vittorio
V
Department of Pharmacology and Human Physiology, University of Bari Medical School, Bari, Italy.
Giordano
Gennaro
G
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Vitalone
Annabella
A
Department of Human Anatomy, Pharmacology and Forensic Sciences, University of Parma Medical School, Parma, Italy.
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005506:Food Contamination; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018675:Toxicity Tests
D008767:Methylmercury Compounds; D011078:Polychlorinated Biphenyls; C004925:methylmercuric chloride; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl