Evidence map›Paper›PMID 40044744›Full record

ArticleScientific reports2025

Dual-directional epi-genotoxicity assay for assessing chemically induced epigenetic effects utilizing the housekeeping TK gene.

Haruto Yamada, Mizuki Odagiri, Keigo Yamakita, Aoi Chiba, Akiko Ukai, Manabu Yasui, Masamitsu Honma, Kei-Ichi Sugiyama, Kiyoe Ura, Akira Sassa

Abstract read
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In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Haruto YamadaDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Mizuki OdagiriDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Keigo YamakitaDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Aoi ChibaDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Akiko UkaiDivision of Genome Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, 210-9501, Kanagawa, Japan.
Manabu YasuiDivision of Genome Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, 210-9501, Kanagawa, Japan. m-yasui@nihs.go.jp.
Masamitsu HonmaDivision of Genome Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, 210-9501, Kanagawa, Japan.
Kei-Ichi SugiyamaDivision of Genome Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, 210-9501, Kanagawa, Japan.
Kiyoe UraDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Akira SassaDepartment of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan. a-sassa@chiba-u.jp.

Funding

Consumer Affairs Agency 24KA1008JSPS 22H03748Ministry of Health, Labor and Welfare 21KA1001
6 · The paper itself

Abstract

Numerous chemicals are associated with carcinogenesis through epigenetic alterations in cells. To detect global epigenetic changes induced by carcinogens, the housekeeping gene can serve as a reporter locus, offering a baseline for identifying shifts in epigenetic marks. To investigate this potential, we developed a simple, cost-effective, and quantitative reporter system to assess chemically induced epigenetic effects, utilizing the thymidine kinase (TK) gene mutation assay as a foundation. Using a standard genotoxicity test cell line, human lymphoblast TK6, we edited the CpG promoter loci of the endogenous TK gene using the CRISPR/dCas9-SunTag-DNMT3A system. This epi-genotoxicity assay, employing modified mTK6 cells, provides a simple method for quantifying chemically induced epigenetic effects. The assay successfully detects both increased TK reversion rates induced by DNMT inhibitors, such as 5-Aza-2'-deoxycytidine and GSK-3484862, and, for the first time, a significant reduction in TK revertant frequency caused by the non-genotoxic carcinogen 12-O-tetradecanoylphorbol-13-acetate (TPA). Chromatin immunoprecipitation and western blotting analyses revealed that TPA treatment led to a global decrease in H3K27Ac levels, likely driven by TPA-mediated inflammation. These results demonstrate the utility of the epi-genotoxicity assay as a valuable tool for evaluating dual-directional epigenetic changes triggered by chemical exposure.

Indexed as

Epigenesis, GeneticGenes, EssentialThymidine KinaseCarcinogensCell LineCRISPR-Cas SystemsDNA MethylationHistonesHumansMutagenicity TestsMutationPromoter Regions, GeneticTetradecanoylphorbol AcetateCarcinogensHistonesTetradecanoylphorbol AcetateThymidine Kinase12-O-tetradecanoylphorbol-13-acetateDNMT inhibitorEpi-genotoxicityReporter assayTK geneToxicology

Identifiers

PMID40044744
PMCPMC11882845

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.