Genotoxicity and mutagenicity of iron and copper in mice

Prá, Daniel; Franke, Silvia Isabel Rech; Giulian, Raquel; Yoneama, M.L.; Dias, Johnny Ferraz; Erdtmann, Bernardo; Henriques, João Antônio Pêgas

doi:10.1007/s10534-007-9118-3

Cited by 81 publications

(33 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with these results, Prá et al (2008) noted that ferrous sulfate induces DNA damage in peripheral blood cells and mouse bone marrow through an increase in the frequency of micronuclei. Clastogenic effects were also induced by ferrous sulfate in a micronucleus assay (Premkumar and Bowlus, 2003) in mouse bone marrow cells.…”

Section: Discussionsupporting

confidence: 77%

Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa)

Alcântara¹,

Ribeiro²,

Matos³

et al. 2013

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Iron is the most important metallic chemical element on Earth. Poisoning caused by excessive iron in humans has been associated with pulmonary diseases including neoplasms caused by inhalation of iron oxides. The involvement of iron in neurodegenerative processes has already been described. DNA alterations are induced by iron and other chemical compounds containing this metal; however, the data are controversial and the mechanism by which iron induces mutagenesis remains unknown. This study assessed in vitro iron-induced cytotoxic and genotoxic responses in an astrocytic cell line. Short-and long-term cytotoxicity and genotoxicity were evaluated with the Cell Proliferation Kit II and micronucleus test, respectively. Results indicated that the highest concentration of iron sulfate tested was cytotoxic in long-term cytotoxic assays and increased micronucleus frequency in comparison to controls. The significant cytotoxicity observed here might be due to the intrinsic ability of iron to induce apoptosis and possible changes in cell cycle kinetics; the genotoxic effects are probably due to the oxidant properties of iron itself. This was the first study to investigate the induction of micronuclei by iron in central nervous system cells.

show abstract

Section: Discussionsupporting

confidence: 77%

Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa)

Alcântara¹,

Ribeiro²,

Matos³

et al. 2013

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Bulky DNA lesions are associated with chromosome breaks and micronuclei frequency (Prá et al 2008). The increase in bone marrow micronuclei frequency in the group of rats treated with sucrose can be related to the capacity of sucrose to induce mutations, as previously observed in the colon of rats treated with sucrose-rich diet (Dragsted et al 2002).…”

Section: Discussionmentioning

confidence: 56%

“…At the end of the experiment, the femurs of the animals were removed and slides were prepared as described by Prá et al (2008). Briefly, bone marrow was mixed with fetal calf serum and smears were prepared with this mixture.…”

Section: Test Of Micronucleus In Bone Marrow Erythrocytesmentioning

confidence: 99%

High consumption of sucrose induces DNA damage in male Wistar rats

Franke

Molz

Mai

et al. 2017

An. Acad. Bras. Ciênc.

Self Cite

View full text Add to dashboard Cite

The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

show abstract

“…An enrichment of aneuploid events in copper may well be due to selection for aneuploidy rather than an increased mutation rate, consistent with the frequent occurrence of additional copies of chrVIII, bearing CUP1. Nevertheless, previous studies with mice have found copper to be mutagenic, using a micronuclei assay that is sensitive to errors in chromosome segregation during mitosis (Prá et al 2008). We thus consider it plausible that the high frequency of aneuploidy observed in this study may have been directly due to copper exposure.…”

Section: Mutagenic Effects Of Coppermentioning

confidence: 52%

Too Much of a Good Thing: The Unique and Repeated Paths Toward Copper Adaptation

Gerstein

Ono

et al. 2014

Genetics

View full text Add to dashboard Cite

Copper is a micronutrient essential for growth due to its role as a cofactor in enzymes involved in respiration, defense against oxidative damage, and iron uptake. Yet too much of a good thing can be lethal, and yeast cells typically do not have tolerance to copper levels much beyond the concentration in their ancestral environment. Here, we report a short-term evolutionary study of Saccharomyces cerevisiae exposed to levels of copper sulfate that are inhibitory to the initial strain. We isolated and identified adaptive mutations soon after they arose, reducing the number of neutral mutations, to determine the first genetic steps that yeast take when adapting to copper. We analyzed 34 such strains through whole-genome sequencing and by assaying fitness within different environments; we also isolated a subset of mutations through tetrad analysis of four lines. We identified a multilayered evolutionary response. In total, 57 single base-pair mutations were identified across the 34 lines. In addition, gene amplification of the copper metallothionein protein, CUP1-1, was rampant, as was chromosomal aneuploidy. Four other genes received multiple, independent mutations in different lines (the vacuolar transporter genes VTC1 and VTC4; the plasma membrane H+-ATPase PMA1; and MAM3, a protein required for normal mitochondrial morphology). Analyses indicated that mutations in all four genes, as well as CUP1-1 copy number, contributed significantly to explaining variation in copper tolerance. Our study thus finds that evolution takes both common and less trodden pathways toward evolving tolerance to an essential, but highly toxic, micronutrient.KEYWORDS Saccharomyces cerevisiae; genetic basis of adaptation; copper tolerance; aneuploidy; CUP1; fitness; parallel adaptation I N his book, Wonderful Life (Gould 1989, p. 51), Stephen J. Gould famously opined that evolution is a historical and contingent process, so much so that "any replay of the tape would lead evolution down a pathway radically different from the road actually taken." While this is undoubtedly true when one considers the full complexity of an organism, refrains are often observed in evolution at the trait level. Repeated evolution, defined as "the independent appearance of similar phenotypic traits in distinct evolutionary lineages" (Gompel and Prud'homme 2009) has been documented in both ecological and clinical environments at all taxonomic levels, e.g., repeated loss of stickleback lateral plates in freshwater (Schluter et al. 2004), ecomorphs of Anolis lizards (Losos 1992), the acquisition of "cystic fibrosis lung" phenotypes in Pseudomonas aeruginosa in patients with cystic fibrosis (Huse et al. 2010), to name but a few. The development of sequencing technologies has recently allowed biologists to ask whether parallel genetic changes underlie observations of parallel phenotypic change. In some cases, parallel phenotypic evolution has been attributed to parallel genotypic evolution, for example, repeated changes to cis-regulatory regions of the same...

show abstract

Genotoxicity and mutagenicity of iron and copper in mice

Cited by 81 publications

References 55 publications

Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa)

Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa)

High consumption of sucrose induces DNA damage in male Wistar rats

Too Much of a Good Thing: The Unique and Repeated Paths Toward Copper Adaptation

Contact Info

Product

Resources

About