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Genotoxicity and mutagenicity of iron and copper in mice

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Abstract

The toxicity of trace metals is still incompletely understood. We have previously shown that a single oral dose of iron or copper induces genotoxic effects in mice in vivo, as detected by single cell gel electrophoresis (comet assay). Here, we report the effect of these metals on subchronic exposure. Mice were gavaged for six consecutive days with either water, 33.2 mg/kg iron, or 8.5 mg/kg copper. On the 7th day, the neutral and alkaline comet assays in whole blood and the bone marrow micronucleus (MN) test were used as genotoxicity and mutagenicity endpoints, respectively. Particle induced X-ray emission was used to determine liver levels of the metals. Females showed a slightly lower DNA damage background, but there was no significant difference between genders for any endpoint. Iron and copper were genotoxic and mutagenic. While copper was more genotoxic in the neutral version, iron was more genotoxic in the alkaline version of the comet assay. Copper induced the highest mutagenicity as evaluated by the MN test. Iron was not mutagenic to male mice. Iron is thought to induce more oxidative lesions than copper, which are primarily detected in the alkaline comet assay. Treatment with iron, but not with copper, induced a significant increase in the hepatic level of the respective metal, reflecting different excretion strategies.

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Acknowledgments

The authors thank Dr Christine C. Gaylarde for critically reading the manuscript. UNISC, CNPq, CAPES and GENOTOX-Royal supported the research.

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Authors and Affiliations

  1. PPG em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil

    Daniel Prá

  2. Curso de Nutrição, Departamento de Educação Física e Saúde, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Rio Grande do Sul, Brazil

    Silvia Isabel Rech Franke

  3. Laboratório de Implantação Iônica, Instituto de Física, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil

    Raquel Giulian, Maria Lúcia Yoneama & Johnny Ferraz Dias

  4. Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Caxias do Sul, Rio Grande do Sul, Brazil

    Bernardo Erdtmann & João Antonio Pêgas Henriques

  5. GENOTOX-Royal/Centro de Biotecnologia do Estado do Rio Grande do Sul (CBIOT), UFRGS, Av. Bento Gonçalves, 9500, Prédio 43421, Campus do Vale, Caixa Postal 15005, CEP 91501-970, Porto Alegre, Rio Grande do Sul, Brazil

    João Antonio Pêgas Henriques

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  1. Daniel Prá
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Correspondence to João Antonio Pêgas Henriques.

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Daniel Prá and Silvia Isabel Rech Franke have contributed equally in conducting the experiment, analyzing data and writing the manuscript.

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Prá, D., Franke, S.I.R., Giulian, R. et al. Genotoxicity and mutagenicity of iron and copper in mice. Biometals 21, 289–297 (2008). https://doi.org/10.1007/s10534-007-9118-3

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