Influence of a mixture of chemical protectors on the lymphoid regeneration of bone marrow and thymus in irradiated mice

Delrez, Marc; Ikeh, V. O.; Maisin, J; Mattelin, G.; Haot, J.; Betz, E.H.

doi:10.1007/bf01922970

Cited by 2 publications

(1 citation statement)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whole body irradiation, such as that occurring prior to bone marrow transplantation, induces thymocyte cell death, peripheral leucopenia and thymic involution. This acute wave of thymocyte death is followed by an acute regrowth of the thymus, termed “thymic rebound” (Delrez et al, 1978). To assess whether IL-6 induced by DNA damage is similarly cytoprotective in this setting, we irradiated wild type and IL-6 -/- mice.…”

Section: Resultsmentioning

confidence: 99%

DNA Damage-Mediated Induction of a Chemoresistant Niche

Gilbert

Hemann

2010

Cell

385

329

View full text Add to dashboard Cite

Summary While numerous cell-intrinsic processes are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the tumor microenvironment on therapeutic outcome. Here, we use a well-established mouse model of Burkitt's lymphoma to show that paracrine factors in the tumor microenvironment modulate lymphoma cell survival following the administration of genotoxic chemotherapy. Specifically, IL-6 and Timp-1 are released in the thymus in response to DNA damage, creating a “chemo-resistant niche” that promotes the survival of a minimal residual tumor burden and serves as a reservoir for eventual tumor relapse. Notably, IL-6 is released acutely from thymic endothelial cells in a p38-dependent manner following genotoxic stress, and this acute secretory response precedes the gradual induction of senescence in tumor-associated stromal cells. Thus, conventional chemotherapies can induce tumor regression while simultaneously eliciting stress responses that protect subsets of tumor cells in select anatomical locations from drug action.

show abstract

Section: Resultsmentioning

confidence: 99%

DNA Damage-Mediated Induction of a Chemoresistant Niche

Gilbert

Hemann

2010

Cell

385

329

View full text Add to dashboard Cite

show abstract

Influence of a Radioprotector WR-638 on the Lymphoid Compartment of the Irradiated Rat Thymus: A Flow Cytometric Analysis

Dragojević-Simić

Čolić

Gašić

1994

International Journal of Radiation Biology

View full text Add to dashboard Cite

The T cell composition of the thymus of X-ray irradiated (3.5 Gy) Wistar rat protected with WR-638 was analyzed by flow cytometry using monoclonal antibodies directed to the Thy 1.1, CD43, CD2, CD5, CD4, CD8 and class I and II MHC antigens. It was shown that this dose of X-rays caused cyclic changes in thymic cellularity manifested as: primary involution (until day 2), primary regeneration (from days 2 to 14), secondary involution (from days 14 to 21) and secondary regeneration (from days 21 to 30). WR-638 reduced the magnitude of thymocyte depletion in the primary involutive phase of the irradiated thymi, primarily as a result of protection of Thy 1.1high+ CD2low+ CD5high+ CD4+ CD8+ class I antigen high+ subpopulations of thymocytes. In the early regenerative phase, WR-638 accelerated the regeneration of CD4-CD8- and CD4-CD8+ thymocyte subsets, followed by subsequent increase of CD4+CD8+ and CD4+CD8- thymocyte subsets. Secondary involutive and regenerative phases in protected animals were characterized by higher absolute cell number of almost all thymocyte subpopulations in comparison with those in irradiated, non-protected animals.

show abstract

Influence of a mixture of chemical protectors on the lymphoid regeneration of bone marrow and thymus in irradiated mice

Cited by 2 publications

References 6 publications

DNA Damage-Mediated Induction of a Chemoresistant Niche

DNA Damage-Mediated Induction of a Chemoresistant Niche

Influence of a Radioprotector WR-638 on the Lymphoid Compartment of the Irradiated Rat Thymus: A Flow Cytometric Analysis

Contact Info

Product

Resources

About