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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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Genome-wide DNA methylation changes in transformed foci induced by nongenotoxic carcinogens

Sung-Hee Hwang1, Hojin Yeom1, Seong Yun Eom1

  • 1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.

Environmental and Molecular Mutagenesis
|March 9, 2019
PubMed

Insights

This study combined cell transformation assays (CTA) with DNA methylation profiling to understand how nongenotoxic carcinogens work. Overlapping methylation changes were found between different carcinogens, suggesting common mechanisms in cancer development.

Area of Science:

  • Toxicology
  • Epigenetics
  • Carcinogenesis

Background:

  • In vitro cell transformation assays (CTA) are used to detect potential nongenotoxic carcinogens.
  • Current CTA protocols lack mechanistic insights into how these agents cause cancer.

Purpose of the Study:

  • To combine in vitro Bhas 42 CTA with DNA methylation profiling.
  • To elucidate the carcinogenic mechanisms of nongenotoxic carcinogens.

Main Methods:

  • Evaluated three nongenotoxic carcinogens: cadmium chloride, methyl carbamate, and lithocholic acid.
  • Utilized sequencing-based DNA methylation profiling on cell clones from CTA.
  • Performed pathway enrichment analysis on differentially methylated regions (DMRs).

Main Results:

  • Cadmium chloride and lithocholic acid showed positive results in Bhas 42 CTA, while methyl carbamate did not.
  • Identified overlapping differentially methylated regions (DMRs) between cadmium chloride and lithocholic acid.
  • Found enrichment of cancer-related pathways (e.g., Wnt signaling) in hypermethylated DMRs.

Conclusions:

  • Genome-wide methylation analysis of CTA-induced foci offers potential for improving CTA methods.
  • Further research is needed to standardize and validate this combined approach for specificity and sensitivity.
  • Nongenotoxic carcinogens may share common epigenetic mechanisms, particularly involving DNA methylation patterns.
Keywords:
In vitro cell transformation assayBhas 42MBD-Seqintegrated approaches to testing and assessment (IATA)methylationnongenotoxic carcinogen

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