Evidence map›Paper›PMID 42223507›Full record

ArticleJournal of occupational health2026

1,2-Dichloropropane, but not dichloromethane or trichloropropane, reduces apoptosis of human cholangiocytes co-cultured with macrophages.

Mst Mahfuza Rahman, Kyoshiro Kusagaya, Cai Zong, Yusuke Kimura, Abigail Ekuban, Ryoya Takizawa, Daichi Nagashima, Alzahraa Fergany, Sahoko Ichihara, Gaku Ichihara

Abstract read
In one paragraph

Article in Journal of occupational health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Mst Mahfuza RahmanDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.
Kyoshiro KusagayaDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.
Cai ZongDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.
Yusuke KimuraDepartment of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan.
Abigail EkubanDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.
Ryoya TakizawaDepartment of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan.
Daichi NagashimaYokohama University of Pharmacy, Japan.
Alzahraa FerganyDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.
Sahoko IchiharaDepartment of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan.ORCID 0000-0002-7224-0949
Gaku IchiharaDepartment of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika, Tokyo 125-8585, Japan.ORCID 0000-0001-5707-5300

Funding

Japan Society for the Promotion of Science 23H03152Japan Society for the Promotion of Science 23 K27842
6 · The paper itself

Abstract

objectivesThe roles of dichloromethane (DCM) and 1,2,3-trichloropropane (1,2,3-TCP) in occupational cholangiocarcinoma, first reported in 2012, remain elusive. This study aimed to determine the potential of 1,2-dichloropropane (1,2-DCP), DCM, and 1,2,3-TCP to induce DNA damage-a hallmark of carcinogenicity-in human cholangiocytes.

methodsMonocultures of human immortalized cholangiocytes (MMNK-1 cholangiocytes) and co-cultures of MMNK-1 cholangiocytes with human THP-1 monocyte-derived macrophages and monocytes were each exposed to 1,2-DCP, DCM or 1,2,3-TCP at 0, 0.1, and 0.4 mM for 24 hours. DNA double-strand break marker γ-H2AX-positive foci and γ-H2AX pan-nuclear staining-which is known to be induced during early or intermediate stages of apoptosis or under replicative stress/checkpoint abrogation in cholangiocytes-were counted in 100 and 200 cholangiocytes, respectively. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining.

resultsThe increase in dense (≥55) γ-H2AX foci induced by all 3 chemical compounds was significantly greater in co-cultures with macrophages, but not with monocytes, than in monocultures. However, only 1,2-DCP decreased the number of γ-H2AX pan-nuclear-positive and TUNEL-positive cholangiocytes in co-cultures with macrophages, but not in monocultured cholangiocytes. Co-treatment with a pan-caspase inhibitor decreased the number of γ-H2AX pan-nuclear-positive cholangiocytes in each group by about 50%, suggesting that apoptotic signaling is involved, at least in part, in the induction of γ-H2AX pan-nuclear-positive cholangiocytes.

conclusionsOur study showed that co-culture with macrophages enhanced DNA double-strand breaks induced by all 3 tested chemical compounds, while only 1,2-DCP exhibited a proliferative effect in monocultures and anti-apoptotic effects in co-cultures with macrophages, which are key characteristics of carcinogens, thus distinguishing 1,2-DCP from DCM and 1,2,3-TCP.

Indexed as

ApoptosisBile DuctsMacrophagesMethylene ChloridePropaneCoculture TechniquesDNA DamageHumans1,2,3-trichloropropaneMethylene ChloridePropanepropylene dichloride1,2,3-trichloropropane1,2-dichloropropaneanti-apoptotic effectcarcinogenicitycholangiocarcinomadichloromethaneDNA damageoccupational cancer

Identifiers

PMID42223507
PMCPMC13335648

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.