Methylmercury genotoxicity: A novel effect in human
cell lines of the central nervous system
María Elena Crespo-López
, Andréa Lima de Sá
, Anderson Manoel Herculano
Rommel Rodríguez Burbano
, José Luiz Martins do Nascimento
Lab. Biologia Celular e Molecular, Núcleo de Medicina Tropical, Universidade Federal do Pará,
Av. Generalíssimo Deodoro 92, Umarizal. 66055-240 Belém-PA, Brazil
Lab. Neuroquímica Molecular e Celular, Dep. Fisiologia, Universidade Federal do Pará Brazil
Lab. Citogenética Humana e Genética Toxicológica, Dep. Biologia; Universidade Federal do Pará,
Rua Augusto Correia 01, 66075-110 Belém-PA, Brazil
Received 31 March 2006; accepted 13 August 2006
Available online 26 September 2006
Methylmercury is an important source of environmental contamination and the central nervous system (CNS) is one of the main target organs.
Methylmercury genotoxicity was already demonstrated in peripherical tissues but was never detected in the brain. Thus, the objective of this work
was to verify its genotoxic effect using brain cell lines. Glioblastoma (U373) and neuroblastoma (B103) human cell lines were exposed to
methylmercury (0–10 μM). By measuring cellular viability, concentrations inducing b 20% of cellular death (P b 0.05) were selected: 1 and
0.1 μM. To detect micronuclei, 200.000 cells were treated with methylmercury for 24 h, and then incubated with cytochalasin B (2 μg/ml) for 72 h
(U373) or 48 h (B103). The binucleation index, frequency of micronucleated cells, micronucleation index, metaphasic index and index of
nucleoplasmic bridges were determined. Statistical analysis showed indices and percentages significantly higher (P b 0.05) in methylmercury-
treated cells. Each cell line was shown to be differently sensitive to each biomarker of genotoxic damage, which seems to indicate the existence of
different mechanisms of toxicity. This work demonstrates, for the first time, MeHg ability to provoke genotoxicity in cells of brain origin with
relatively low levels of exposure.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Genotoxicity; Mercury; Methylmercury; Neurotoxicity; Micronucleus; Microtubules; Biomarker
Mercury represents a diffused and hazardous environmental
contaminant, its capacity of bioaccumulation and biomagnifica-
tion in the food chain increases the risk of human exposure. In
nature, mercury compounds can undergo processes of transfor-
mation which convert them into different inorganic and organic
forms (Eisler, 2004; Crespo-López et al., 2005). In comparative
studies with different mercury species, methylmercury (MeHg)
has been revealed as the most toxic form of mercury (Toimela
and Tähti, 2004; Silva-Pereira et al., 2005).
Toxicological studies about human methylmercury exposure
have demonstrated that central nervous system (CNS) is a target
organ for mercury toxicity (Mottet et al., 1984). This fact can be
associated to MeHg ability to easily cross through the blood-
brain barrier, thus accumulating in different brain areas as the
cerebellum, brain cortex and retina (Mottet et al., 1984; Erie
et al., 2005).
MeHg exposure induces different patterns of changes in the
CNS. For example, mercury poisoning in the adult brain is
characterized by damage of very localized anatomical areas of
the visual cortex and neuronal loss of the granule layer of the
cerebellum. However, immature CNS, which is extremely sen-
sitive to MeHg neurotoxicity, shows a diffuse and widespread
disorganization of the cerebral cortex cytoarchitecture with
disappearance of granule cells (Vettori et al., 2003). These
alterations could be associated with failures in the normal
pattern of cellular division induced by MeHg exposure during
CNS development (Vettori et al., 2003).
Environment International 33 (2007) 141 – 146
Corresponding author. Tel./fax: +55 91 32410032.
E-mail address: email@example.com (M.E. Crespo-López).
0160-4120/$ - see front matter © 2006 Elsevier Ltd. All rights reserved.