Evidence map›Paper›PMID 34087939›Full record

ArticleRadiation research2021

Radiation-Induced Senescence in p16+/LUC Mouse Lung Compared to Bone Marrow Multilineage Hematopoietic Progenitor Cells.

Michael W Epperly, Donna Shields, Renee Fisher, Wen Hou, Hong Wang, Diala Fatima Hamade, Amitava Mukherjee, Joel S Greenberger

Open access · greenAbstract read
In one paragraph

Article in Radiation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Radiation-induced senescence: therapeutic opportunities.Radiation oncology (London, England) · 2023
    Review
  5. Article
  6. Article
  7. 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

8 authors at 2 institutions in 1 country.

Michael W EpperlyDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Donna ShieldsDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Renee FisherDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Wen HouDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Hong WangDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
Diala Fatima HamadeDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Amitava MukherjeeDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
Joel S GreenbergerDepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232.
UPMC Hillman Cancer Center · USUniversity of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Training and EducationU19AI068021 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GREENBERGER, JOEL S · 2005 to 2019
$44.4M
LR-IL-22 for Mitigation and Management of Radiation InjuriesU01AI172885 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOEL S GREENBERGER · 2023 to 2026
$2.4M
NCI NIH HHS P30 CA047904NIAID NIH HHS U01 AI172885NIAID NIH HHS U19 AI068021
6 · The paper itself

Abstract

We defined the time course of ionizing radiation-induced senescence in lung compared to bone marrow of p16+/LUC mice in which the senescence-induced biomarker (p16) is linked to a luciferase reporter gene. Periodic in situ imaging revealed increased luciferase activity in the lungs of 20 Gy thoracic irradiated, but not 8 Gy total-body irradiated (TBI) mice beginning at day 75 and increasing to day 170. In serial sections of explanted lungs, senescent cells appeared in the same areas as did fibrosis in the 20 Gy thoracic irradiated, but not the 8 Gy TBI group. Lungs from 8 Gy TBI mice at one year did show increased RNA levels for p16, p21, p19 and TGF-β. Individual senescent cells in 20 Gy irradiated mouse lung included those with epithelial, endothelial, fibroblast and hematopoietic cell biomarkers. Rare senescent cells in the lungs of 8 Gy TBI mice at one year were of endothelial phenotype. Long-term bone marrow cultures (LTBMCs) were established at either day 60 or one year after 8 Gy TBI. In freshly removed marrow at both times after irradiation, there were increased senescent cells. In LTBMCs, there were increased senescent cells in both weekly harvested single cells and in colonies of multilineage hematopoietic progenitor cells producing CFU-GEMM (colony forming unit-granulocyte, erythrocyte, monocyte/macrophage, mega-karyocyte) that were formed in secondary cultures when these single cells were plated in semisolid media. LTBMCs from TBI mice produced fewer CFU-GEMM; however, the relative percentage of senescent cell-containing colonies was increased as measured by both p16-luciferase and β-galactosidase. Therefore, 20 Gy thoracic radiation, as well as 8 Gy TBI, induces senescent cells in the lungs. With bone marrow, 8 Gy TBI induced senescence in both hematopoietic cells and in colony-forming progenitors. The p16+/LUC mouse strain provides a valuable system in which to compare the kinetics of radiation-induced senescence between organs in vivo, and to evaluate the potential role of senescent cells in irradiation pulmonary fibrosis.

Indexed as

AnimalsBone MarrowCell LineageCells, CulturedCellular SenescenceColony-Forming Units AssayCyclin-Dependent Kinase Inhibitor p16Genes, p16Hematopoietic Stem CellsLuciferasesLungMiceMice, Inbred C57BLMultipotent Stem CellsPulmonary FibrosisRadiation Injuries, ExperimentalCyclin-Dependent Kinase Inhibitor p16LuciferasesRecombinant Fusion Proteins

Identifiers

PMID34087939
PMCPMC8456367
OpenAlexW3164422380

What OpenQuestion holds

Textmetadata
LicenceTDM
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.