PittsburghV1, Main, Exploration, bibRecord, 001801

Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2−/−) Mice

Identifieur interne : 001801 ( Main/Exploration ); précédent : 001800; suivant : 001802

Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2−/−) Mice

Auteurs : Hebist Berhane [États-Unis] ; Michael W. Epperly [États-Unis] ; Julie Goff [États-Unis] ; Ronny Kalash [États-Unis] ; Shaonan Cao [États-Unis] ; Darcy Franicola [États-Unis] ; Xichen Zhang [États-Unis] ; Donna Shields [États-Unis] ; Frank Houghton [États-Unis] ; Hong Wang [États-Unis] ; Peter Wipf [États-Unis] ; Kalindi Parmar [États-Unis] ; Joel S. Greenberger [États-Unis]

Source :

Radiation research [ 0033-7587 ] ; 2014.

RBID : PMC:3970166

Descripteurs français

English descriptors

KwdEn :
- Animals, Antioxidants (metabolism), Cell Cycle (drug effects), Cell Cycle (radiation effects), Cell Line, Fanconi Anemia (metabolism), Fanconi Anemia (pathology), Fanconi Anemia Complementation Group D2 Protein (deficiency), Free Radical Scavengers (pharmacology), Granulocyte-Macrophage Progenitor Cells (metabolism), Hematopoiesis (drug effects), Hematopoiesis (radiation effects), Hematopoietic Stem Cells (drug effects), Hematopoietic Stem Cells (metabolism), Hematopoietic Stem Cells (pathology), Hematopoietic Stem Cells (radiation effects), Humans, Interleukin-3 (pharmacology), Mesenchymal Stromal Cells (drug effects), Mesenchymal Stromal Cells (metabolism), Mesenchymal Stromal Cells (pathology), Mesenchymal Stromal Cells (radiation effects), Mice, Mitochondria (drug effects), Mitochondria (metabolism), Mitochondria (radiation effects), Nitrogen Oxides (pharmacology), Oxidative Stress (drug effects), Oxidative Stress (radiation effects), Radiation Tolerance, Reactive Oxygen Species (metabolism), Time Factors.
MESH :
- chemical , deficiency : Fanconi Anemia Complementation Group D2 Protein.
- chemical , metabolism : Antioxidants, Reactive Oxygen Species.
- drug effects : Cell Cycle, Hematopoiesis, Hematopoietic Stem Cells, Mesenchymal Stromal Cells, Mitochondria, Oxidative Stress.
- metabolism : Fanconi Anemia, Granulocyte-Macrophage Progenitor Cells, Hematopoietic Stem Cells, Mesenchymal Stromal Cells, Mitochondria.
- pathology : Fanconi Anemia, Hematopoietic Stem Cells, Mesenchymal Stromal Cells.
- chemical , pharmacology : Free Radical Scavengers, Interleukin-3, Nitrogen Oxides.
- radiation effects : Cell Cycle, Hematopoiesis, Hematopoietic Stem Cells, Mesenchymal Stromal Cells, Mitochondria, Oxidative Stress.
- Animals, Cell Line, Humans, Mice, Radiation Tolerance, Time Factors.

Abstract

FancD2 plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. Fancd2^−/− mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in Fancd2^−/− mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and radiosensitivity in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines. We further evaluated radioprotection by a mitochondrial-targeted antioxidant GS-nitroxide, JP4-039. Hematopoiesis longevity in Fancd2^−/− mouse long-term marrow cultures was diminished and bone marrow stromal cell lines were radiosensitive compared to Fancd2^+/+ stromal cells (Fancd2^−/− D₀ = 1.4 ± 0.1 Gy, ñ = 5.0 ± 0.6 vs. Fancd2^+/+ D₀ = 1.6 ± 0.1 Gy, ñ = 6.7 ± 1.6), P = 0.0124 for D₀ and P = 0.0023 for ñ, respectively). In contrast, Fancd2^−/− IL-3-dependent hematopoietic progenitor cells were radioresistant (D₀ = 1.71 ± 0.04 Gy and ñ = 5.07 ± 0.52) compared to Fancd2^+/+ (D₀ = 1.39 ± 0.09 Gy and ñ = 2.31 ± 0.85, P = 0.001 for D₀). CFU-GM from freshly explanted Fancd2^−/− marrow was also radioresistant. Consistent with radiosensitivity, irradiated Fancd2^−/− stromal cells had higher DNA damage by comet tail intensity assay compared to Fancd2^+/+ cells (P < 0.0001), slower DNA damage recovery, lower baseline total antioxidant capacity, enhanced radiation-induced depletion of antioxidants, and increased CDKN1A-p21 gene transcripts and protein. Consistent with radioresistance, Fancd2^−/− IL-3-dependent hematopoietic cells had higher baseline and post irradiation total antioxidant capacity. While, there was no detectable alteration of radiation-induced cell cycle arrest with Fancd2^−/− stromal cells, hematopoietic progenitor cells showed reduced G₂/M cell cycle arrest. The absence of the mouse Fancd2 gene product confers radiosensitivity to bone marrow stromal but not hematopoietic progenitor cells.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970166

DOI: 10.1667/RR13405.1
PubMed: 24397476
PubMed Central: 3970166

Affiliations:

Le document en format XML

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</italic>
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<author><name sortKey="Zhang, Xichen" sort="Zhang, Xichen" uniqKey="Zhang X" first="Xichen" last="Zhang">Xichen Zhang</name>
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<author><name sortKey="Houghton, Frank" sort="Houghton, Frank" uniqKey="Houghton F" first="Frank" last="Houghton">Frank Houghton</name>
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<author><name sortKey="Wang, Hong" sort="Wang, Hong" uniqKey="Wang H" first="Hong" last="Wang">Hong Wang</name>
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<term>Antioxidants (metabolism)</term>
<term>Cell Cycle (drug effects)</term>
<term>Cell Cycle (radiation effects)</term>
<term>Cell Line</term>
<term>Fanconi Anemia (metabolism)</term>
<term>Fanconi Anemia (pathology)</term>
<term>Fanconi Anemia Complementation Group D2 Protein (deficiency)</term>
<term>Free Radical Scavengers (pharmacology)</term>
<term>Granulocyte-Macrophage Progenitor Cells (metabolism)</term>
<term>Hematopoiesis (drug effects)</term>
<term>Hematopoiesis (radiation effects)</term>
<term>Hematopoietic Stem Cells (drug effects)</term>
<term>Hematopoietic Stem Cells (metabolism)</term>
<term>Hematopoietic Stem Cells (pathology)</term>
<term>Hematopoietic Stem Cells (radiation effects)</term>
<term>Humans</term>
<term>Interleukin-3 (pharmacology)</term>
<term>Mesenchymal Stromal Cells (drug effects)</term>
<term>Mesenchymal Stromal Cells (metabolism)</term>
<term>Mesenchymal Stromal Cells (pathology)</term>
<term>Mesenchymal Stromal Cells (radiation effects)</term>
<term>Mice</term>
<term>Mitochondria (drug effects)</term>
<term>Mitochondria (metabolism)</term>
<term>Mitochondria (radiation effects)</term>
<term>Nitrogen Oxides (pharmacology)</term>
<term>Oxidative Stress (drug effects)</term>
<term>Oxidative Stress (radiation effects)</term>
<term>Radiation Tolerance</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Antioxydants (métabolisme)</term>
<term>Anémie de Fanconi (anatomopathologie)</term>
<term>Anémie de Fanconi (métabolisme)</term>
<term>Cellules souches hématopoïétiques ()</term>
<term>Cellules souches hématopoïétiques (anatomopathologie)</term>
<term>Cellules souches hématopoïétiques (effets des radiations)</term>
<term>Cellules souches hématopoïétiques (métabolisme)</term>
<term>Cellules stromales mésenchymateuses ()</term>
<term>Cellules stromales mésenchymateuses (anatomopathologie)</term>
<term>Cellules stromales mésenchymateuses (effets des radiations)</term>
<term>Cellules stromales mésenchymateuses (métabolisme)</term>
<term>Cycle cellulaire ()</term>
<term>Cycle cellulaire (effets des radiations)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Facteurs temps</term>
<term>Humains</term>
<term>Hématopoïèse ()</term>
<term>Hématopoïèse (effets des radiations)</term>
<term>Interleukine-3 (pharmacologie)</term>
<term>Lignée cellulaire</term>
<term>Mitochondries ()</term>
<term>Mitochondries (effets des radiations)</term>
<term>Mitochondries (métabolisme)</term>
<term>Oxydes d'azote (pharmacologie)</term>
<term>Piégeurs de radicaux libres (pharmacologie)</term>
<term>Progéniteurs des granulocytes et macrophages (métabolisme)</term>
<term>Protéine du groupe de complémentation D2 de l'anémie de Fanconi (déficit)</term>
<term>Radiotolérance</term>
<term>Souris</term>
<term>Stress oxydatif ()</term>
<term>Stress oxydatif (effets des radiations)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Fanconi Anemia Complementation Group D2 Protein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antioxidants</term>
<term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Anémie de Fanconi</term>
<term>Cellules souches hématopoïétiques</term>
<term>Cellules stromales mésenchymateuses</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Cycle</term>
<term>Hematopoiesis</term>
<term>Hematopoietic Stem Cells</term>
<term>Mesenchymal Stromal Cells</term>
<term>Mitochondria</term>
<term>Oxidative Stress</term>
</keywords>
<keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Protéine du groupe de complémentation D2 de l'anémie de Fanconi</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des radiations" xml:lang="fr"><term>Cellules souches hématopoïétiques</term>
<term>Cellules stromales mésenchymateuses</term>
<term>Cycle cellulaire</term>
<term>Hématopoïèse</term>
<term>Mitochondries</term>
<term>Stress oxydatif</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fanconi Anemia</term>
<term>Granulocyte-Macrophage Progenitor Cells</term>
<term>Hematopoietic Stem Cells</term>
<term>Mesenchymal Stromal Cells</term>
<term>Mitochondria</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antioxydants</term>
<term>Anémie de Fanconi</term>
<term>Cellules souches hématopoïétiques</term>
<term>Cellules stromales mésenchymateuses</term>
<term>Espèces réactives de l'oxygène</term>
<term>Mitochondries</term>
<term>Progéniteurs des granulocytes et macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Fanconi Anemia</term>
<term>Hematopoietic Stem Cells</term>
<term>Mesenchymal Stromal Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Interleukine-3</term>
<term>Oxydes d'azote</term>
<term>Piégeurs de radicaux libres</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Free Radical Scavengers</term>
<term>Interleukin-3</term>
<term>Nitrogen Oxides</term>
</keywords>
<keywords scheme="MESH" qualifier="radiation effects" xml:lang="en"><term>Cell Cycle</term>
<term>Hematopoiesis</term>
<term>Hematopoietic Stem Cells</term>
<term>Mesenchymal Stromal Cells</term>
<term>Mitochondria</term>
<term>Oxidative Stress</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Humans</term>
<term>Mice</term>
<term>Radiation Tolerance</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules souches hématopoïétiques</term>
<term>Cellules stromales mésenchymateuses</term>
<term>Cycle cellulaire</term>
<term>Facteurs temps</term>
<term>Humains</term>
<term>Hématopoïèse</term>
<term>Lignée cellulaire</term>
<term>Mitochondries</term>
<term>Radiotolérance</term>
<term>Souris</term>
<term>Stress oxydatif</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1"><italic>FancD2</italic>
 plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. <italic>Fancd2<sup>−/−</sup>
</italic>
 mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in <italic>Fancd2<sup>−/−</sup>
</italic>
 mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and radiosensitivity in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines. We further evaluated radioprotection by a mitochondrial-targeted antioxidant GS-nitroxide, JP4-039. Hematopoiesis longevity in <italic>Fancd2<sup>−/−</sup>
</italic>
 mouse long-term marrow cultures was diminished and bone marrow stromal cell lines were radiosensitive compared to <italic>Fancd2<sup>+/+</sup>
</italic>
 stromal cells (<italic>Fancd2<sup>−/−</sup>
</italic>
 D<sub>0</sub>
 = 1.4 ± 0.1 Gy, ñ = 5.0 ± 0.6 vs. <italic>Fancd2<sup>+/+</sup>
</italic>
 D<sub>0</sub>
 = 1.6 ± 0.1 Gy, ñ = 6.7 ± 1.6), <italic>P</italic>
 = 0.0124 for D<sub>0</sub>
 and <italic>P</italic>
 = 0.0023 for ñ, respectively). In contrast, <italic>Fancd2<sup>−/−</sup>
</italic>
 IL-3-dependent hematopoietic progenitor cells were radioresistant (D<sub>0</sub>
 = 1.71 ± 0.04 Gy and ñ = 5.07 ± 0.52) compared to <italic>Fancd2<sup>+/+</sup>
</italic>
 (D<sub>0</sub>
 = 1.39 ± 0.09 Gy and ñ = 2.31 ± 0.85, <italic>P</italic>
 = 0.001 for D<sub>0</sub>
). CFU-GM from freshly explanted <italic>Fancd2<sup>−/−</sup>
</italic>
 marrow was also radioresistant. Consistent with radiosensitivity, irradiated <italic>Fancd2<sup>−/−</sup>
</italic>
 stromal cells had higher DNA damage by comet tail intensity assay compared to <italic>Fancd2<sup>+/+</sup>
</italic>
 cells (<italic>P</italic>
 < 0.0001), slower DNA damage recovery, lower baseline total antioxidant capacity, enhanced radiation-induced depletion of antioxidants, and increased CDKN1A-p21 gene transcripts and protein. Consistent with radioresistance, <italic>Fancd2<sup>−/−</sup>
</italic>
 IL-3-dependent hematopoietic cells had higher baseline and post irradiation total antioxidant capacity. While, there was no detectable alteration of radiation-induced cell cycle arrest with <italic>Fancd2<sup>−/−</sup>
</italic>
 stromal cells, hematopoietic progenitor cells showed reduced G<sub>2</sub>
/M cell cycle arrest. The absence of the mouse <italic>Fancd2</italic>
 gene product confers radiosensitivity to bone marrow stromal but not hematopoietic progenitor cells.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Pennsylvanie</li>
</region>
<settlement><li>Pittsburgh</li>
</settlement>
<orgName><li>Université de Pittsburgh</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Berhane, Hebist" sort="Berhane, Hebist" uniqKey="Berhane H" first="Hebist" last="Berhane">Hebist Berhane</name>
</region>
<name sortKey="Cao, Shaonan" sort="Cao, Shaonan" uniqKey="Cao S" first="Shaonan" last="Cao">Shaonan Cao</name>
<name sortKey="Epperly, Michael W" sort="Epperly, Michael W" uniqKey="Epperly M" first="Michael W." last="Epperly">Michael W. Epperly</name>
<name sortKey="Franicola, Darcy" sort="Franicola, Darcy" uniqKey="Franicola D" first="Darcy" last="Franicola">Darcy Franicola</name>
<name sortKey="Goff, Julie" sort="Goff, Julie" uniqKey="Goff J" first="Julie" last="Goff">Julie Goff</name>
<name sortKey="Greenberger, Joel S" sort="Greenberger, Joel S" uniqKey="Greenberger J" first="Joel S." last="Greenberger">Joel S. Greenberger</name>
<name sortKey="Houghton, Frank" sort="Houghton, Frank" uniqKey="Houghton F" first="Frank" last="Houghton">Frank Houghton</name>
<name sortKey="Kalash, Ronny" sort="Kalash, Ronny" uniqKey="Kalash R" first="Ronny" last="Kalash">Ronny Kalash</name>
<name sortKey="Parmar, Kalindi" sort="Parmar, Kalindi" uniqKey="Parmar K" first="Kalindi" last="Parmar">Kalindi Parmar</name>
<name sortKey="Shields, Donna" sort="Shields, Donna" uniqKey="Shields D" first="Donna" last="Shields">Donna Shields</name>
<name sortKey="Wang, Hong" sort="Wang, Hong" uniqKey="Wang H" first="Hong" last="Wang">Hong Wang</name>
<name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name>
<name sortKey="Zhang, Xichen" sort="Zhang, Xichen" uniqKey="Zhang X" first="Xichen" last="Zhang">Xichen Zhang</name>
</country>
</tree>
</affiliations>
</record>

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Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2−/−) Mice

Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2−/−) Mice

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