Is Low Non-Lethal Concentration of Methylmercury Really Safe? A Report on Genotoxicity with Delayed Cell Proliferation.
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.
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
María Elena
ME
Crespo-Lopez
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Allan
A
Costa-Malaquias
Laboratório de Cultura de Tecidos e Citogenética, Departamento de Meio Ambiente, Instituto Evandro Chagas, 67030-000 Ananindeua (Pará), Brasil.
Edivaldo H C
EH
Oliveira
Laboratório de Fertilização In Vitro, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Moysés S
MS
Miranda
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Gabriela P F
GP
Arrifano
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
José R
JR
Souza-Monteiro
Laboratório de Cultura de Tecidos e Citogenética, Departamento de Meio Ambiente, Instituto Evandro Chagas, 67030-000 Ananindeua (Pará), Brasil.
Fernanda Espirito-Santo
FE
Sagica
Laboratório de Farmacologia da Inflamação e do Comportamento, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Enéas A
EA
Fontes-Junior
Laboratório de Farmacologia da Inflamação e do Comportamento, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Cristiane S F
CS
Maia
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
Barbarella M
BM
Macchi
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém (Pará), Brasil.
José Luiz M
JL
do Nascimento
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats
D008767:Methylmercury Compounds; D009153:Mutagens