This SuperSeries is composed of the SubSeries listed below.
Purpose: Historically, the Syrian Hamster Embryo - cell transformation assay (SHE-CTA) has provided a method to predict the carcinogenicity of test chemicals. Note that the cells harvested for the SHE-CTA are from fetuses at gestation day 13.5 and not from embryos as historically recorded. This method has been criticized for insufficient mechanistic understanding and subjective assessment of colonies morphological transformation. A more objective method is needed that additionally provides mode of action information. A possible mode of action of carcinogens includes disruption of DNA methylation in gene regulatory regions and consequent changes in gene expression. Such genetic loci could provide biomarkers to assist in predicting the carcinogenicity of both genotoxic and non-genotoxic chemicals acting through DNA methylation disruption.
More...This SuperSeries is composed of the SubSeries listed below.
Purpose: Historically, the Syrian Hamster Embryo - cell transformation assay (SHE-CTA) has provided a method to predict the carcinogenicity of test chemicals. Note that the cells harvested for the SHE-CTA are from fetuses at gestation day 13.5 and not from embryos as historically recorded. This method has been criticized for insufficient mechanistic understanding and subjective assessment of colonies morphological transformation. A more objective method is needed that additionally provides mode of action information. A possible mode of action of carcinogens includes disruption of DNA methylation in gene regulatory regions and consequent changes in gene expression. Such genetic loci could provide biomarkers to assist in predicting the carcinogenicity of both genotoxic and non-genotoxic chemicals acting through DNA methylation disruption.
Overall design: Refer to individual Series
This series of experiments evaluates the use of reduced representation bisulfite sequencing and RNA-seq to discover biomarkers to predict carcinogenicity. Syrian Hamster fetal cells (SHF) were obtained using previously developed and validated methods [OECD, 2015. Guidance document on the in vitro Syrian hamster embryo (SHE) cell transformation assay. Series on Testing & Assessment No. 214, 1-24]. The protocol described by Pickles et. al (2016) was adapted to 1) treat SHF cells with (B[a]P) or vehicle control (DMSO), 2) collect morphologically transformed (MTc) and normal (Nc) colonies, and 3) to expand colony-derived cultures to senescence (SEN) and beyond (SENbp).
Less...| Accession | PRJNA909278; GEO: GSE220238 |
| Type | Umbrella project |
| Publications | - Desaulniers D et al., "DNA methylation changes from primary cultures through senescence-bypass in Syrian hamster fetal cells initially exposed to benzo[a]pyrene.", Toxicology, 2023 Mar 15;487:153451
- Meier MJ et al., "Dataset on DNA methylation and gene expression changes induced by 5-aza-2'-deoxycytidine in Syrian golden hamster fetal cell cultures.", Data Brief, 2023 Jun;48:109097
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| Submission | Registration date: 6-Dec-2022
Mechanistic Studies Division Genomics Laboratory, Health Canada, Government of Canada |
| Relevance | Superseries |
Project Data:
| Resource Name | Number
of Links |
|---|
| Sequence data |
| SRA Experiments | 69 |
| Publications |
| PubMed | 2 |
| PMC | 1 |
| Other datasets |
| BioSample | 69 |
| GEO DataSets | 4 |
DNA methylation changes from primary cultures through senescence-bypass in Syrian hamster fetal cells initially exposed to benzo[a]pyrene encompasses the following 3 sub-projects:
| Project Type | Number of Projects |
| Epigenomics | 2 |
BioProject
accession | Organism | Title |
|---|
| PRJNA604968 | Mesocricetus auratus | Chronology of DNA methylation changes through transformation stage leading to senescence by-pass in Syrian hamster fetal primary cells exposed to benzo[a]pyrene (Mechanistic Studies Division...) | | PRJNA604960 | Mesocricetus auratus | DNA methylation in Syrian hamster female fetal cells (gestation day 13.5) exposed in vitro to 5-aza-2’deoxycytidine (5aCdR) (Mechanistic Studies Division...) |
|
| Other | 1 |
BioProject
accession | Name | Title |
|---|
| PRJNA906121 | Finding genetic loci that are sensitive to demethylation to assist in the development of DNA methylation-based in vitro assay for the identification of carcinogens | Finding genetic loci that are sensitive to demethylation to assist in the development of DNA methylation-based in vitro assay for the identification of carcinogens (Mechanistic Studies Division...) |
|