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.
Highlights
Mercury exposure is a serious public health problem worldwide
This study demonstrated that exposure to a low, sublethal and non-apoptotic concentration of methylmercury causes significant genotoxicity and disturbances of the cell cycle and proliferation in cells of glial origin
Exposure of C6 cells to MeHg for 24 h showed an LC50 of 6.08 μM (Fig 2), a similar value to those previously described in other cell lines or primary cultures of CNS [8, 11, 21, 22]
Summary
Mercury exposure is a serious public health problem worldwide. In 2013, Brazil, along with 91 countries, signed the Convention of Minamata (www.mercuryconvention.org), with the aim of reducing and combating environmental and human exposure to this metal. In recent decades, concerns have been raised, since chronic exposure to relatively low levels of methylmercury (MeHg), the most toxic compound of mercury, can be found in regions as the Seychelles or the Amazon Basin, with contaminated fish as the main source responsible for human exposure [5,6,7]. This type of intoxication activates several cellular mechanisms that can potentially lead to long-term deleterious consequences, most importantly genotoxicity [8, 9]. It is currently unknown as to whether exposure to low levels of mercury below established limits is safe
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
