Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing

Abstract

a b s t r a c tCell 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.

Toxicological assessment of silica-coated iron oxide nanoparticles in human astrocytes

“…In that case, S-ION exposure did alter the repair of H 2 O 2 -induced DNA damage in these cells, with considerably more pronounced effects when serum-free medium was employed. This dissimilar response to S-ION exposure of the two types of nervous system cells indicates, as previously reported, that glioma cells have a more efficient repair capability of induced DNA damage than neurons(Laffon et al, 2017).All genotoxicity results together indicate that S-ION present a low genotoxic activity, limited to easily repairable DNA damage as demonstrated by the positive results obtained in comet assay together with the negative results from γH2AX and MN assays. In any case, the DNA damage induced by S-ION seems to be repaired, since the repair capacity resulted not altered, and, consequently, it was not fixed in the cells as proved by the lack of MN , all these effects were not dependent on the presence/absence of serum in the medium.Nevertheless, the quantity of iron ions released from the S-ION depended markedly on the medium composition.…”

Salivary leucocytes as suitable biomatrix for the comet assay in human biomonitoring studies

“…In all cases, cells exposed to these three genotoxic agents showed dose-dependent increases of primary DNA damage, regardless the cell sample employed, demonstrating the sensitivity of all these samples to the induction of genetic damage from different origin and their suitability for the comet assay procedure. Besides, response of the different biomatrices, i.e., salivary leucocytes, both fresh and frozen, and frozen PBL, to the three types of genetic insults was quite similar to one another, and consistent with a number of previous studies evaluating the effects of the same genotoxic agents on different cell types (Collins et al 1997;Laffon et al 2017;Valdiglesias et al 2020). Furthermore, comparing the baseline level of primary DNA damage (Fig.…”

“…Fresh and frozen saliva leucocytes and frozen PBL were exposed to four well-known DNA damaging agents: MMS, Act-D, ultraviolet (UV) radiation, and KBrO 3 . The doses used, as well as the treatment times, were selected on the basis of previous studies (Collins et al 1997;Sánchez-Flores et al 2015;Laffon et al 2017;Møller et al 2020b).…”

Evaluation of cytotoxicity and genotoxicity induced by oleic acid‐coated iron oxide nanoparticles in human astrocytes

“…This different response between the two types of nervous system cells are in line with the well‐accepted idea that glial cells may have a more efficient repair ability in order to protect neuronal tissue from external insults (Saeed et al ). However, it may be also due to the less sensitivity to this type of DNA damage induction of glial cells when compared to neurons, as previously demonstrated (Laffon et al ).…”