Methylmercury genotoxicity: A novel effect in human cell lines of the central nervous system María Elena Crespo-López a, ⁎ , Andréa Lima de Sá a , Anderson Manoel Herculano b , Rommel Rodríguez Burbano c , José Luiz Martins do Nascimento b a Lab. Biologia Celular e Molecular, Núcleo de Medicina Tropical, Universidade Federal do Pará, Av. Generalíssimo Deodoro 92, Umarizal. 66055-240 Belém-PA, Brazil b Lab. Neuroquímica Molecular e Celular, Dep. Fisiologia, Universidade Federal do Pará Brazil c 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 Abstract 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 1. Introduction 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 www.elsevier.com/locate/envint ⁎ Corresponding author. Tel./fax: +55 91 32410032. E-mail address: ecrespo@ufpa.br (M.E. Crespo-López). 0160-4120/$ - see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.envint.2006.08.005