Is Low Non-Lethal Concentration of Methylmercury Really Safe? A Report on Genotoxicity with Delayed Cell Proliferation

PLoS One. 2016 Sep 13;11(9):e0162822. doi: 10.1371/journal.pone.0162822. eCollection 2016.

Abstract

Human exposure to relatively low levels of methylmercury is worrying, especially in terms of its genotoxicity. It is currently unknown as to whether exposure to low levels of mercury (below established limits) is safe. Genotoxicity was already shown in lymphocytes, but studies with cells of the CNS (as the main target organ) are scarce. Moreover, disturbances in the cell cycle and cellular proliferation have previously been observed in neuronal cells, but no data are presently available for glial cells. Interestingly, cells of glial origin accumulate higher concentrations of methylmercury than those of neuronal origin. Thus, the aim of this work was to analyze the possible genotoxicity and alterations in the cell cycle and cell proliferation of a glioma cell line (C6) exposed to a low, non-lethal and non-apoptotic methylmercury concentration. Biochemical (mitochondrial activity) and morphological (integrity of the membrane) assessments confirmed the absence of cell death after exposure to 3 μM methylmercury for 24 hours. Even without promoting cell death, this treatment significantly increased genotoxicity markers (DNA fragmentation, micronuclei, nucleoplasmic bridges and nuclear buds). Changes in the cell cycle profile (increased mitotic index and cell populations in the S and G2/M phases) were observed, suggesting arrest of the cycle. This delay in the cycle was followed, 24 hours after methylmercury withdrawal, by a decrease number of viable cells, reduced cellular confluence and increased doubling time of the culture. Our work demonstrates that exposure to a low sublethal concentration of MeHg considered relatively safe according to current limits promotes genotoxicity and disturbances in the proliferation of cells of glial origin with sustained consequences after methylmercury withdrawal. This fact becomes especially important, since this cellular type accumulates more methylmercury than neurons and displays a vital role protecting the CNS, especially in chronic intoxication with this heavy metal.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Damage
  • Humans
  • Methylmercury Compounds / administration & dosage
  • Methylmercury Compounds / toxicity*
  • Mutagenicity Tests
  • Mutagens / administration & dosage
  • Mutagens / toxicity*
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Rats

Substances

  • Methylmercury Compounds
  • Mutagens

Grants and funding

This work was supported by Conselho Nacional de Ciência e Tecnologia em Pesquisa (CNPq, Brazil; grants 467143/2014-5 and 447568/2014-0) and Instituto Evandro Chagas (IEC, Brazil). J.L.M. do Nascimento, E.H.C. Oliveira and M.E. Crespo-López thank CNPq for their CNPq fellowships. Also, A. Costa-Malaquias, J.R. Souza-Monteiro and G.P.F. Arrifano thank Fundação de Amparo à Pesquisa do Estado do Pará (FAPESPA, Brazil) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES, Brazil) for their PhD fellowships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.