Use of the Syrian Hamster Embryo Cell Transformation Assay for Determining the Carcinogenic Potential of Heavy Metal Compounds

Kerckaert, Gary A.; LeBoeuf, Robert A.; Isfort, Robert J.

doi:10.1006/faat.1996.0176

Cited by 37 publications

(5 citation statements)

References 19 publications

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“…Although, epidemiological, animal, and cell culture studies have found nickel compounds to be carcinogenic [14], [25]–[27], the precise mechanism(s) of nickel carcinogenesis is not well understood. The carcinogenic properties of nickel may be attributable in part, to activation and/or repression of gene expression induced by changes in the DNA methylation status and histone tail post-translational modifications.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

et al. 2011

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Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3), a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s) underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq) and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq). The effect of NiCl2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs) on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl2. This study may provide insights into the epigenetic mechanism(s) underlying the carcinogenicity of nickel compounds.

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Section: Discussionmentioning

confidence: 99%

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

et al. 2011

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“…The cell transformation assay (CTA) is an in vitro approach that makes us of the phenotypic transformation of cells as a marker of carcinogenicity [ 143 , 144 ]. Cells transformed in vitro have been shown to induce tumors when injected into immunosuppressed animals.…”

Section: Carcinogenicitymentioning

confidence: 99%

Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment—A Review

et al. 2020

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Changes in the genetic material can lead to serious human health defects, as mutations in somatic cells may cause cancer and can contribute to other chronic diseases. Genotoxic events can appear at both the DNA, chromosomal or (during mitosis) whole genome level. The study of mechanisms leading to genotoxicity is crucially important, as well as the detection of potentially genotoxic compounds. We consider the current state of the art and describe here the main endpoints applied in standard human in vitro models as well as new advanced 3D models that are closer to the in vivo situation. We performed a literature review of in vitro studies published from 2000–2020 (August) dedicated to the genotoxicity of nanomaterials (NMs) in new models. Methods suitable for detection of genotoxicity of NMs will be presented with a focus on advances in miniaturization, organ-on-a-chip and high throughput methods.

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“…28 Although, epidemiological, animal, and cell culture studies have found nickel compounds to be carcinogenic, the mechanism(s) of nickel carcinogenesis require additional research. [29][30][31][32] Since the mutagenic activity of nickel compounds in mutation assays from Salmonella to mammalian cells in vitro has been low it has been suggested that nickel-induced mutagenic activity is not the underlying mechanism in nickel induced carcinogenesis. [33][34][35][36] Instead, numerous studies have implicated structural alterations in chromatin and epigenetic changes as the primary events in nickel carcinogenesis.…”

Section: Nickelmentioning

confidence: 99%

Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium

2009

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SummaryAlthough carcinogenic metals have been known to disrupt a wide range of cellular processes the precise mechanism by which these exert their carcinogenic effects is not known. Over the last decade or two, studies in the field of metal carcinogenesis suggest that epigenetic mechanisms may play a role in metal-induced carcinogenesis. In this review we summarize the evidence demonstrating that exposure to carcinogenic metals such as nickel, arsenic, chromium, and cadmium can perturb DNA methylation levels as well as global and gene specific histone tail posttranslational modification marks. We also wish to emphasize the importance in understanding that gene expression can be regulated by both genetic and epigenetic mechanisms and both these must be considered when studying the mechanism underlying the toxicity and cell-transforming ability of carcinogenic metals and other toxicants, and aberrant changes in gene expression that occur during disease states such as cancer.

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Use of the Syrian Hamster Embryo Cell Transformation Assay for Determining the Carcinogenic Potential of Heavy Metal Compounds

Cited by 37 publications

References 19 publications

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment—A Review

Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium

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