Evidence map›Paper›PMID 28728135›Full record

ArticleEnvironmental health perspectives2017

Prostate Cancer Risk and DNA Methylation Signatures in Aging Rats following Developmental BPA Exposure: A Dose-Response Analysis.

Gail S Prins, Shu-Hua Ye, Lynn Birch, Xiang Zhang, Ana Cheong, Han Lin, Esther Calderon-Gierszal, Jacob Groen, Wen-Yang Hu, Shuk-Mei Ho and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Environmental health perspectives, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% of its field
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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. A systematic review of metabolomics biomarkers for Bisphenol A exposure.Metabolomics : Official journal of the Metabolomic Society · 2018
    Pooled it
  2. Review
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  9. Review
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  11. Bibliometric Analysis of the Toxicity of Bisphenol A.International journal of environmental research and public health · 2022
    Review
  12. Article
  13. Article
  14. Review
  15. Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland.International journal of environmental research and public health · 2021
    Review
  16. The regulation mechanisms and the Lamarckian inheritance property of DNA methylation in animals.Mammalian genome : official journal of the International Mammalian Genome Society · 2021
    Review
  17. Review
  18. Article
  19. Article
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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

11 authors at 3 institutions in 1 country.

Gail S PrinsDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Shu-Hua YeDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Lynn BirchDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Xiang ZhangDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Ana CheongDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Han LinDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Esther Calderon-GierszalDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Jacob GroenDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Wen-Yang HuDepartment of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
Shuk-Mei HoDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Richard B van BreemenDepartment of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
University of Illinois Chicago · USUniversity of Cincinnati Medical Center · USUniversity of Cincinnati · US

Funding

REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI YADAV, JAGJIT S · 1992 to 2022
$35.4M
PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HAISENLEDER, DANIEL J. · 1998 to 2013
$16.5M
Pilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6M
Epigenetic Basis for Prostate Carcinogenesis following Early Estrogenic ExposuresR01ES015584 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI HO, SHUK-MEI, PRINS, GAIL S · 2008 to 2012
$3.1M
Developmental Exposure to Low-dose Bisphenol A and Human Prostate Cancer SusceptiRC2ES018758 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI HO, SHUK-MEI, PRINS, GAIL S · 2009 to 2010
$1.9M
Estrogen Receptors in Human Prostate Stem-Progenitor CellsR01CA172220 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PRINS, GAIL S · 2013 to 2017
$1.7M
Prostatic Effects of Chronic Exposure to Bisphenol A in a Rat ModelU01ES020886 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PRINS, GAIL S · 2011 to 2014
$878k
NCI NIH HHS R01 CA172220NICHD NIH HHS U54 HD028934NIEHS NIH HHS P30 ES006096NIEHS NIH HHS P30 ES027792NIEHS NIH HHS R01 ES015584NIEHS NIH HHS RC2 ES018758NIEHS NIH HHS U01 ES020886
6 · The paper itself

Abstract

backgroundPrevious studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment.

objectivesA complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes.

methodsMale neonatal Sprague-Dawley rats were briefly exposed to 0.1 to 5,000 μg BPA/kg BW on postnatal days (PND) 1, 3, and 5. Individual prostate lobes plus periurethral prostatic ducts were evaluated at 7 mo or 1 y of age without or with adult testosterone plus estradiol (T+E) to promote carcinogenesis. DNA methylation of five genes was quantified by bisulfite genomic sequencing in d-200 dorsal prostates across BPA doses. Serum free-BPA and BPA-glucuronide were quantitated in sera of individual PND 3 pups collected 1 hr postexposure utilizing ultra-high-pressure tandem mass spectrometry (UHPLC-MS-MS).

resultsThe lowest BPA dose initiated maximal hormonal carcinogenesis in lateral prostates despite undetectable free BPA 1 hr postexposure. Further, prostatic intraepithelial neoplasia (PIN) progressed to carcinoma in rats given neonatal low-dose BPA with adult T+E but not in rats given adult T+E alone. The dorsal and ventral lobes and periurethral prostatic ducts exhibited a nonmonotonic dose response with peak PIN, proliferation and apoptotic values at 10–100 μg/kg BW. This was paralleled by nonmonotonic and dose-specific DNA hypomethylation of genes that confer carcinogenic risk, with greatest hypomethylation at the lowest BPA doses.

conclusionsDevelopmental BPA exposures heighten prostate cancer susceptibility in a complex dose- and lobe-specific manner. Importantly, elevated carcinogenic risk is found at doses that yield undetectable serum free BPA. Dose-specific epigenetic modifications of selected genes provide a mechanistic framework that may connect early-life BPA to later-life predisposition to prostate carcinogenesis. https://doi.org/10.1289/EHP1050.

Indexed as

AgingDNA MethylationAnimalsBenzhydryl CompoundsBisphenol A CompoundsChromatography, High Pressure LiquidDose-Response Relationship, DrugEnvironmental PollutantsIncidenceMalePhenolsProstatic NeoplasmsRatsRats, Sprague-DawleyTandem Mass SpectrometryBenzhydryl Compoundsbisphenol ABisphenol A CompoundsEnvironmental PollutantsPhenols

Identifiers

PMID28728135
PMCPMC5744650
OpenAlexW2738481576

What OpenQuestion holds

Textmetadata
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.