Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing.
Cell cultures from neuronal and glial origin have proven to be powerful tools for elucidating cellular and molecular mechanisms of nervous system development and physiology, and as neurotoxicity models to evaluate in vitro the possible effects of chemicals. But cellular heterogeneity of nervous system is considerable and these cells have been shown to respond diversely to neurotoxic insults, leading to disparate results from different studies. To shed more light on suitability of cellular models of nervous origin for neurotoxicity screening, the objective of this study was to compare the sensitivity to genetic damage induction of two nervous cell lines. To this aim, neurons (SH-SY5Y) and glial (A172) cells were treated with differently-acting genotoxic agents (bleomycin, actinomycin-D, methyl methanesulfonate, mitomycin C, and griseofulvin). After discarding cytotoxicity, genotoxicity was evaluated by a battery of assays encompassing detection of different genetic lesions. Results obtained showed that glial cells are generally more resistant to genotoxic damage induced by clastogenic agents, but more sensitive to aneugenic effects. These results highlight the need of proper design of in vitro neurotoxicology studies, especially for neurogenotoxicity screening, emphasizing the importance of employing more than one nervous cell type for testing the potential toxicity of a particular exposure.
Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Spain.
Blanca
B
Laffon
Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Spain.
Natalia
N
Fernández-Bertólez
EPIUnit. Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, nº 135, 4050-600 Porto, Portugal.
Carla
C
Costa
Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Spain.
Eduardo
E
Pásaro
Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Spain; EPIUnit. Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, nº 135, 4050-600 Porto, Portugal. Electronic address: vvaldiglesias@udc.es.
Vanessa
V
Valdiglesias
D001761:Bleomycin / Q000633:toxicity; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D003609:Dactinomycin / Q000633:toxicity; D006118:Griseofulvin / Q000633:toxicity; D006801:Humans; D008741:Methyl Methanesulfonate / Q000633:toxicity; D015162:Micronucleus Tests / Q000379:methods; D016685:Mitomycin / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000473:pathology*
D009153:Mutagens; D001761:Bleomycin; D003609:Dactinomycin; D006118:Griseofulvin; D016685:Mitomycin; D008741:Methyl Methanesulfonate
A172 cells; Comet assay; Micronucleus test; Neurogenotoxicity; SH-SY5Y cells; γH2AX assay