Effect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis.

2.50
Hdl Handle:
http://hdl.handle.net/10541/88616
Title:
Effect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis.
Authors:
Hoyes, Katherine P; Cai, W B; Potten, Christopher S; Hendry, Jolyon H
Abstract:
PURPOSE: Overexpression of bcl-2 protects against radiation induced apoptosis in lymphohaematopoietic cell types in vivo, whilst bcl-2 deficiency radiosensitizes murine T-lymphocytes in vitro. However, there are few data regarding the influence of bcl-2 deficiency on the radiosensitivity of non-lymphoid cell types. The purpose of this study was to investigate the role of bcl-2 in the clonogenic radiation response of intestinal crypts, bone marrow progenitor cells and testicular stem cells. METHOD: Survival curves were obtained for each cell type from bcl-2 null (-/-), heterozygote (+/-) and wild type (+/+) mice. Crypt survival in the small and large intestine was assessed using the crypt microcolony assay. Committed haemopoietic progenitors were assayed using in vitro colony-forming cell (CFC) assays and survival of clonogenic spermatogonia was assessed by scoring regenerative tubules at 35 days post-irradiation. RESULTS: There was no difference in small intestine crypt survival between the three genotypes. In the colon, there was a tendency towards lower clonogen survival in the +/- and -/- animals. Haemopoietic in vitro CFC from -/- animals showed lower survival in comparison to +/+ mice, but spermatogonial stem cells were comparatively more radioresistant. CONCLUSIONS: Deficiencies in bcl-2 affect the radiation response of different cell populations in small but different ways. This may be due to variations between cells in their innate capacity for apoptosis, their dependence on different members of the bcl-2 family gene and their cell-cycle status and p53 expression.
Affiliation:
CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, UK. khoyes@picr.man.ac.uk
Citation:
Effect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis. 2000, 76 (11):1435-42 Int. J. Radiat. Biol.
Journal:
International Journal of Radiation Biology
Issue Date:
Nov-2000
URI:
http://hdl.handle.net/10541/88616
DOI:
10.1080/09553000050176199
PubMed ID:
11098846
Type:
Article
Language:
en
ISSN:
0955-3002
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHoyes, Katherine Pen
dc.contributor.authorCai, W Ben
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorHendry, Jolyon Hen
dc.date.accessioned2009-12-29T10:25:58Z-
dc.date.available2009-12-29T10:25:58Z-
dc.date.issued2000-11-
dc.identifier.citationEffect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis. 2000, 76 (11):1435-42 Int. J. Radiat. Biol.en
dc.identifier.issn0955-3002-
dc.identifier.pmid11098846-
dc.identifier.doi10.1080/09553000050176199-
dc.identifier.urihttp://hdl.handle.net/10541/88616-
dc.description.abstractPURPOSE: Overexpression of bcl-2 protects against radiation induced apoptosis in lymphohaematopoietic cell types in vivo, whilst bcl-2 deficiency radiosensitizes murine T-lymphocytes in vitro. However, there are few data regarding the influence of bcl-2 deficiency on the radiosensitivity of non-lymphoid cell types. The purpose of this study was to investigate the role of bcl-2 in the clonogenic radiation response of intestinal crypts, bone marrow progenitor cells and testicular stem cells. METHOD: Survival curves were obtained for each cell type from bcl-2 null (-/-), heterozygote (+/-) and wild type (+/+) mice. Crypt survival in the small and large intestine was assessed using the crypt microcolony assay. Committed haemopoietic progenitors were assayed using in vitro colony-forming cell (CFC) assays and survival of clonogenic spermatogonia was assessed by scoring regenerative tubules at 35 days post-irradiation. RESULTS: There was no difference in small intestine crypt survival between the three genotypes. In the colon, there was a tendency towards lower clonogen survival in the +/- and -/- animals. Haemopoietic in vitro CFC from -/- animals showed lower survival in comparison to +/+ mice, but spermatogonial stem cells were comparatively more radioresistant. CONCLUSIONS: Deficiencies in bcl-2 affect the radiation response of different cell populations in small but different ways. This may be due to variations between cells in their innate capacity for apoptosis, their dependence on different members of the bcl-2 family gene and their cell-cycle status and p53 expression.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCell Survival-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshGenes, bcl-2-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshIntestine, Large-
dc.subject.meshIntestine, Small-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Knockout-
dc.subject.meshRadiation Tolerance-
dc.subject.meshStem Cells-
dc.subject.meshTestis-
dc.titleEffect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis.en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, UK. khoyes@picr.man.ac.uken
dc.identifier.journalInternational Journal of Radiation Biologyen

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