Evidence map›Paper›PMID 40902835›Full record

ArticleToxicology letters2025

Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism.

Tessa C A van Tongeren, Susan J Hall, Samantha J Madnick, Blanche C Ip, Paul L Carmichael, Hequn Li, Wei Chen, Lori A Breitweiser, Heather E Pence, David M Ames and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicology letters, 2025. 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

16 authors.

Tessa C A van TongerenDivision of Toxicology, Wageningen University and Research, Wageningen 6700 EA, the Netherlands. Electronic address: tcavantongeren@gmail.com.
Susan J HallDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Samantha J MadnickDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA; Center for Alternatives to Animals in Testing, Brown University, Providence, RI, USA.
Blanche C IpDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA; Center for Alternatives to Animals in Testing, Brown University, Providence, RI, USA.
Paul L CarmichaelUnilever Safety and Environmental Assurance Centre, Sharnbrook, Bedfordshire MK44 1LQ, UK.
Hequn LiUnilever Safety and Environmental Assurance Centre, Sharnbrook, Bedfordshire MK44 1LQ, UK.
Wei ChenCorteva, Inc., Indianapolis, IN, USA.
Lori A BreitweiserCorteva, Inc., Indianapolis, IN, USA.
Heather E PenceCorteva, Inc., Indianapolis, IN, USA.
David M AmesCorteva, Inc., Indianapolis, IN, USA.
Andrew J BowlingCorteva, Inc., Indianapolis, IN, USA.
Kamin J JohnsonCorteva, Inc., Indianapolis, IN, USA.
Richard CubberleyUnilever Safety and Environmental Assurance Centre, Sharnbrook, Bedfordshire MK44 1LQ, UK.
Bruce SherfINDIGO Biosciences, Inc., State Collage, PA, USA.
Jeffrey R MorganDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA; Center for Alternatives to Animals in Testing, Brown University, Providence, RI, USA.
Kim BoekelheideDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA; Center for Alternatives to Animals in Testing, Brown University, Providence, RI, USA. Electronic address: kim_Boekelheide@brown.edu.

Funding

UTERINE NK CELL HOMING FROM THE PERIPHERAL CIRCULATIONP20RR018728 · NCRR · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI MARSIT, CARMEN JOSEPH · 2003 to 2011
$16.7M
Center for Cancer Signaling NetworksP30GM103410 · NIGMS · BROWN UNIVERSITY · PI ATWOOD, WALTER J · 2012 to 2015
$4.3M
CENTER FOR CANCER SIGNALING NETWORKSP30RR031153 · NCRR · BROWN UNIVERSITY · PI ATWOOD, WALTER J · 2011 to 2011
$1.1M
Shared High-throughput DNA sequencer for the Brown University CommunityS10RR027634 · NCRR · BROWN UNIVERSITY · PI WESSEL, GARY M · 2010 to 2010
$500k
NCRR NIH HHS P20 RR018728NCRR NIH HHS P30 RR031153NCRR NIH HHS S10 RR027634NIGMS NIH HHS P30 GM103410
6 · The paper itself

Abstract

For the in vitro determination of toxicity on target organs in the presence of physiologically relevant human metabolism, we recently developed a two-chamber liver-target organ co-culture system in a medium-throughput 96-well format. Our proof-of-concept study using human HepaRG microtissues cultured in three-dimension (3D) and AR-CALUX reporter cells demonstrated the significantly reduced testosterone (T)-mediated androgen receptor (AR) responses in the presence of human liver metabolism. The present study further increased the scientific confidence in this two-chamber co-culture system as a flexible and robust tool to capture androgen-mediated responses by incorporating alternate AR reporter cell systems as the target and examining additional androgenic compounds. The system generated concordant metabolism-dependent changes in T- and 5α-dihydrotestosterone (DHT)-mediated AR responses using two different AR reporter cell systems (AR-CALUX, AR-INDIGO). The AR reporters had different sensitivity ranges and required media optimization. We demonstrated that this two-chamber co-culture system with integrated hepatic biotransformation can be used to evaluate endocrine activity with potential metabolism modulation of parent compounds.

Indexed as

AndrogensHepatocytesLiverReceptors, AndrogenTestosteroneBiotransformationCell LineCoculture TechniquesDihydrotestosteroneGenes, ReporterHumansAndrogensAR protein, humanDihydrotestosteroneReceptors, AndrogenTestosterone3D HepaRG microtissuesAR-CALUXAR-INDIGOin vitro testingToxicity testing

Identifiers

PMID40902835
PMCPMC13354927

What OpenQuestion holds

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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.