PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model
Joint Authors
Rondelli, Catherine M.
Larsen, Michele Campaigne
N’jai, Alhaji
Czuprynski, Charles J.
Jefcoate, Colin R.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2015), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-11-07
Country of Publication
Egypt
No. of Pages
12
Abstract EN
7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM) leading to mature cell losses as replenishment fails.
These losses are mediated by Cyp1b1, independent of the AhR, despite induction of Cyp1b1.
BM mesenchymal progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is minimally induced.
PreB colony forming unit activity (PreB CFU) is lost within 24 hours in isolated BM cells (BMC) unless cocultured with cells derived from primary MPC (BMS2 line).
The mouse embryonic OP9 line, which provides more efficient coculture support, shares similar induction-resistant Cyp1b1 characteristics.
This OP9 support is suppressed by DMBA, which is then prevented by Cyp1b1 inhibitors.
OP9-enriched medium partially sustains CFU activities but loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1.
PreB CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA.
BMC gene expression profiles identified cytokines and developmental factors that are substantially changed in Cyp1b1-ko mice.
DMBA had few effects in WT mice but systematically modified many clustered responses in Cyp1b1-ko mice.
Typical BMC AhR-responsive genes were insensitive to Cyp1b1 deletion.
TCDD replicated Cyp1b1 interventions, suggesting alternative AhR mediation.
Cyp1b1 also diminishes oxidative stress, a key cause of stem cell instability.
American Psychological Association (APA)
Rondelli, Catherine M.& Larsen, Michele Campaigne& N’jai, Alhaji& Czuprynski, Charles J.& Jefcoate, Colin R.. 2016. PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model. Stem Cells International،Vol. 2016, no. 2016, pp.1-12.
https://search.emarefa.net/detail/BIM-1116125
Modern Language Association (MLA)
Rondelli, Catherine M.…[et al.]. PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model. Stem Cells International Vol. 2016, no. 2016 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1116125
American Medical Association (AMA)
Rondelli, Catherine M.& Larsen, Michele Campaigne& N’jai, Alhaji& Czuprynski, Charles J.& Jefcoate, Colin R.. PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model. Stem Cells International. 2016. Vol. 2016, no. 2016, pp.1-12.
https://search.emarefa.net/detail/BIM-1116125
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1116125