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Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: Impact of DNA repair.
- Source :
- International Journal of Radiation Biology; Jul2008, Vol. 84 Issue 7, p533-548, 16p, 1 Color Photograph, 1 Diagram, 1 Chart, 6 Graphs
- Publication Year :
- 2008
-
Abstract
- Purpose: To ask whether highly metastatic sublines show more marked low-dose hyper-radiosensitivity (HRS) response than poorly metastatic ones. Materials and methods: The progressive (PRO) subline showing tumourigenicity and metastatic potential and the regressive (REG) subline showing neither tumourigenicity nor metastatic potential were both isolated from a parental rat colon tumour. Clonogenic survival, micronuclei and apoptosis, cell cycle distribution, DNA single- (SSB) and double-strand breaks (DSB) induction and repair were examined. Results: HRS phenomenon was demonstrated in PRO subline. Before irradiation, PRO cells show more spontaneous damage than REG cells. After 0.1 Gy, PRO cells displayed: (i) More DNA SSB 15 min post-irradiation, (ii) more unrepaired DNA DSB processed by the non-homologous end-joining (NHEJ) and by the RAD51-dependent recombination pathways, (iii) more micronuclei, than REG cells while neither apoptosis nor p53 phosphorylation nor cell cycle arrest was observed in both sublines. Conclusions: HRS response of PRO subline may be induced by impairments in NHEJ repair that targets G1 cells and RAD51-dependent repair that targets S-G2/M cells. The cellular consequences of such impairments are a failure to arrest in cell cycle, the propagation of damage through cell cycle, mitotic death but not p53-dependent apoptosis. Tumourigenic cells with high metastatic potential may preferentially show HRS response. [ABSTRACT FROM AUTHOR]
- Subjects :
- COLON tumors
DNA repair
RADIOACTIVITY
RATS
METASTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 09553002
- Volume :
- 84
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- International Journal of Radiation Biology
- Publication Type :
- Academic Journal
- Accession number :
- 33325212
- Full Text :
- https://doi.org/10.1080/09553000802195331