Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/88619
Title:
Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation.
Authors:
Hendry, Jolyon H; Broadbent, D A; Roberts, Stephen A; Potten, Christopher S
Abstract:
PURPOSE: To study the role of p53 and bcl-2 in the response of the small intestine to irradiation delivered at low dose-rate. MATERIALS AND METHODS: Mice homozygous for p53 or bcl-2 deletion (-/-), their respective heterozygotes (+/-), and their wild-type littermates (+/+) including a previously used hybrid strain (B6D2F1), were irradiated to the whole-body using 60Co gamma-rays at 1 Gy h(-1). Crypt survival levels in the small intestine were measured at day 3 after the end of irradiation. RESULTS: Crypt survival levels were higher in p53 -/- mice than in the other p53 genotypes after 25-30 Gy, but not after lower or higher doses. Similar experiments with the three genotypes for bcl-2 status showed lower crypt survival after all doses used in the -/- mice, compared with the +/- and +/+ mice, which were similar in response. The marked degree of curvature in the survival curve observed for the p53 genotypes was also observed in B6D2F1 hybrid mice, was particularly striking in the p53 -/- mice, but was not seen to the same extent in the bcl-2 genotypes. The heterozygotes for p53 or for bcl-2 were nearer in response to their respective +/+ genotypes rather than the -/- genotypes. CONCLUSION: The increased crypt survival levels at some radiation dose levels in the p53 nulls contrasts with the lack of change reported previously using irradiation at high dose-rate. The decreased survival in the bcl-2 nulls is consistent with the known 'survival' function of bcl-2, although bcl-2 expression has not been detected immunohistochemically in this intestinal site. The marked degree of curvature in the dose-response curve at high dose levels for some genotypes was unexpected at this low dose-rate.
Affiliation:
Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK. JHendry@PICR.MAN.AC.UK
Citation:
Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation. 2000, 76 (4):559-65 Int. J. Radiat. Biol.
Journal:
International Journal of Radiation Biology
Issue Date:
Apr-2000
URI:
http://hdl.handle.net/10541/88619
DOI:
10.1080/095530000138574
PubMed ID:
10815637
Type:
Article
Language:
en
ISSN:
0955-3002
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHendry, Jolyon Hen
dc.contributor.authorBroadbent, D Aen
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorPotten, Christopher Sen
dc.date.accessioned2009-12-29T10:42:32Z-
dc.date.available2009-12-29T10:42:32Z-
dc.date.issued2000-04-
dc.identifier.citationEffects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation. 2000, 76 (4):559-65 Int. J. Radiat. Biol.en
dc.identifier.issn0955-3002-
dc.identifier.pmid10815637-
dc.identifier.doi10.1080/095530000138574-
dc.identifier.urihttp://hdl.handle.net/10541/88619-
dc.description.abstractPURPOSE: To study the role of p53 and bcl-2 in the response of the small intestine to irradiation delivered at low dose-rate. MATERIALS AND METHODS: Mice homozygous for p53 or bcl-2 deletion (-/-), their respective heterozygotes (+/-), and their wild-type littermates (+/+) including a previously used hybrid strain (B6D2F1), were irradiated to the whole-body using 60Co gamma-rays at 1 Gy h(-1). Crypt survival levels in the small intestine were measured at day 3 after the end of irradiation. RESULTS: Crypt survival levels were higher in p53 -/- mice than in the other p53 genotypes after 25-30 Gy, but not after lower or higher doses. Similar experiments with the three genotypes for bcl-2 status showed lower crypt survival after all doses used in the -/- mice, compared with the +/- and +/+ mice, which were similar in response. The marked degree of curvature in the survival curve observed for the p53 genotypes was also observed in B6D2F1 hybrid mice, was particularly striking in the p53 -/- mice, but was not seen to the same extent in the bcl-2 genotypes. The heterozygotes for p53 or for bcl-2 were nearer in response to their respective +/+ genotypes rather than the -/- genotypes. CONCLUSION: The increased crypt survival levels at some radiation dose levels in the p53 nulls contrasts with the lack of change reported previously using irradiation at high dose-rate. The decreased survival in the bcl-2 nulls is consistent with the known 'survival' function of bcl-2, although bcl-2 expression has not been detected immunohistochemically in this intestinal site. The marked degree of curvature in the dose-response curve at high dose levels for some genotypes was unexpected at this low dose-rate.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAnimals-
dc.subject.meshCell Survival-
dc.subject.meshDose-Response Relationship, Radiation-
dc.subject.meshIntestine, Small-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.subject.meshRadiation Tolerance-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleEffects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation.en
dc.typeArticleen
dc.contributor.departmentExperimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK. JHendry@PICR.MAN.AC.UKen
dc.identifier.journalInternational Journal of Radiation Biologyen

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