Genomic Integrity of Mouse Embryonic Stem Cells

Leyns, Luc; Gonzalez, Laetitia

doi:10.5772/37327

Cited by 3 publications

(3 citation statements)

References 85 publications

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“…Mutations in germ and stem cells are potentially more serious than those in other cells as they are passed to the cells’ progeny within the developing embryo or regenerating tissue ( 216 , 217 ). There is a presumed survival benefit when stem cells tend to show a particularly stringent maintenance of genome integrity through cell cycle regulation and enhanced responses to DNA damage ( 218 ).…”

Section: Resultsmentioning

confidence: 99%

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Goodson¹,

Lowe

Carpenter

et al. 2015

CARCIN

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252

167

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Section: Resultsmentioning

confidence: 99%

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Goodson¹,

Lowe

Carpenter

et al. 2015

CARCIN

Self Cite

252

167

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show abstract

“…Interestingly, comparing 2D and 3D models, differences were reported in toxicity induced by single‐walled carbon nanotubes (SWCNT) , while for silica NPs a distinct genotoxic response was shown in both models . In vitro stem cell differentiation seems to be an adequate model as they allow simultaneous assessment of these different parameters . Moreover, as in this cell model, the effects will depend on the proportion of heterogeneity of the cell type within the cell populations studied; the cell type and kinetics are of critical importance.…”

Section: Future Perspectives In Nano‐genotoxicologymentioning

confidence: 99%

Towards a New Paradigm in Nano‐Genotoxicology: Facing Complexity of Nanomaterials’ Cellular Interactions and Effects

Gonzalez¹,

Cundari

Leyns³

et al. 2017

Basic Clin Pharma Tox

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Changes in paradigm contribute to advances in research. The current paradigms for the evaluation of toxicity of chemicals refer to linear or curvilinear dose-response curves with or without threshold and to surface-dependent induction of oxidative damage for particles. The unique physicochemical properties and biological/genotoxic activity of engineered nanomaterials (NMs) require the development of a new paradigm. Because of their unusual dosimetry and their multiple interactions at NM level (agglomeration/aggregation) and at different cellular and extracellular levels, NMs are likely to have complex modes of action (multiple hits at multiple targets) leading to complex thresholded-non-thresholded dose-response curves. Understanding their cellular targets and their modes of action will contribute to the production of safe-by-design NMs. An integrative, cell-bycell approach for genotoxic effects should be applied to tackle this emerging paradigm in nano-genotoxicology.

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“…Mutation frequencies are generally much lower in stem cells compared with somatic cells, for example, 100-1000 times lower in mouse embryonic stem cells compared with embryonic fibroblasts (204). This more stringent maintenance of genomic integrity in stem cells is the consequence of differences in cell cycle regulation and increased DNA repair capacity (205). Besides differences in cell cycle checkpoints and repair, two other ways to deal with DNA damage for embryonic stem cells are the induction of apoptosis or the process of differentiation in order to avoid passing mutations to their progeny.…”

Section: Stem Cellsmentioning

confidence: 99%

Causes of genome instability: the effect of low dose chemical exposures in modern society

Langie¹,

Koppen²,

Desaulniers

et al. 2015

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175

114

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Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

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Genomic Integrity of Mouse Embryonic Stem Cells

Cited by 3 publications

References 85 publications

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Towards a New Paradigm in Nano‐Genotoxicology: Facing Complexity of Nanomaterials’ Cellular Interactions and Effects

Causes of genome instability: the effect of low dose chemical exposures in modern society

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