Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts

Dikomey, Ekkehard; Borgmann, Kerstin; Brammer, I.; Kasten-Pisula, Ulla

doi:10.1016/s0300-483x(03)00293-2

Cited by 41 publications

(19 citation statements)

References 120 publications

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“…It has been previously demonstrated that mitotic cell death induced by ionizing radiation correlates with nonrepairable DNA damage (27). The analysis of the results presented herein reveals that nonrepairable or slowly rejoined DSBs would be an indicator of mitotic cell death, in agreement with previous reports that showed a correlation between the radiosensitivity of different human cell lines, tumors, and normal tissues and the residual level of gH2AX or the rate of loss of gH2AX (17,28).…”

Section: Discussionsupporting

confidence: 91%

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Ibañez

Bracalente

Molinari

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionsupporting

confidence: 91%

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Ibañez

Bracalente

Molinari

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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“…During the last 10 years, huge effort has been invested to find biomarkers in patient-derived cells which might enable the pre-therapeutic prediction of individual clinical radiosensitivity. Some promising candidates have been published like apoptosis/necrosis [32,33], double-strand breaks [12], micronuclei [16] or chromosome aberrations [7].…”

Section: Introductionmentioning

confidence: 99%

Multicentric investigation of ionising radiation-induced cell death as a predictive parameter of individual radiosensitivity

Greve

Dreffke

Rickinger³

et al. 2009

Apoptosis

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In the present study, the predictive value of ionising radiation (IR)-induced cell death was tested in peripheral blood lymphocytes (PBLs) and their corresponding Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) in an interlaboratory comparison. PBLs and their corresponding LCLs were derived from 15 tumour patients, that were considered clinically radiosensitive based on acute side-effects, and matched controls. Upon coding of the samples, radiosensitivity of the matched pairs was analysed in parallel in three different laboratories by assessing radiation-induced apoptotic and necrotic cell death using annexin V. All participating laboratories detected a dose-dependent increase of apoptosis and necrosis in the individual samples, to a very similar extent. However, comparing the mean values of apoptotic and necrotic levels derived from PBLs of the radiosensitive cohort with the mean values of the control cohort did not reveal a significant difference. Furthermore, within 15 matched pairs, no sample was unambiguously and independently identified by all three participating laboratories to demonstrate in vitro hypersensitivity that matched the clinical hypersensitivity. As has been reported previously, apoptotic and necrotic cell death is barely detectable in immortalised LCL derivatives using low doses of IR. Concomitantly, the differences in apoptosis or necrosis levels found in primary cells of different individuals were not observed in the corresponding LCL derivatives. All participating laboratories concordantly reasoned that, with the methods applied here, IR-induced cell death in PBLs is unsuitable to unequivocally predict the individual clinical radiosensitivity of cancer patients. Furthermore, LCLs do not reflect the physiological properties of the corresponding primary blood lymphocytes with regard to IR-induced cell death. Their value to predict clinical radiosensitivity is thus highly questionable.

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“…In the present work, we propose an original strategy for identification of genes and gene regulatory pathways related to the resistance or susceptibility of cells to radiation damage. It has been reported that multiple genetic factors may modulate the occurrence and magnitude of the arrest in the G 1 phase of the cell cycle following exposure to ionizing radiation in human tumour cell lines [14,15]. The ability to G 1 arrest after exposure to gamma rays has been reported for the NCI 60 tumoral cell lines [16].…”

Section: Introductionmentioning

confidence: 99%

Identification of genes involved in radiation‐induced G₁ arrest

Musumarra

Salinaro

Scirè

et al. 2007

Journal of Chemometrics

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The advent of microarray gene expression technology permits the simultaneous analysis of the levels of expression of thousands of genes and provides large dataset requiring multivariate analysis tools. Multiple genetic factors may modulate the occurrence and magnitude of the arrest in the G 1 phase of the cell cycle following exposure to ionizing radiation in human tumour cell lines. The ability to G 1 arrest after exposure to gamma rays and the global gene expression profile, evaluated by cDNA microarray technology, have been reported for the National Cancer Institute (NCI) 60 tumour cell lines panel. The sensitivity of the tumour cell lines to radiations represents an activity fingerprinting that can be correlated by partial least squares (PLS) to the transcriptional profiles of the same cell lines. VIP values obtained by the PLS method are able to detect transcripts relevant to the radiation-induced G 1 arrest. High VIP values were obtained for the basal levels of transcripts such as p21/Waf1/Cip1 and MDM2, that are well known for their roles in G 1 arrest after irradiation. Novel functional relationships suggested by high VIP values can be investigated experimentally. As an example, in the present study, we report that the transcript for the FLJ11046 protein is induced dose-dependently by gamma-irradiation in a cell line with mutated p53, but not in cell lines with wild-type p53. Moreover specific silencing of FLJ11046 transcript by RNA interference technology results in a block of cell growth.

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Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts

Cited by 41 publications

References 120 publications

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Multicentric investigation of ionising radiation-induced cell death as a predictive parameter of individual radiosensitivity

Identification of genes involved in radiation‐induced G₁ arrest

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Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts

Cited by 41 publications

References 120 publications

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Induction and Rejoining of DNA Double Strand Breaks Assessed by H2AX Phosphorylation in Melanoma Cells Irradiated with Proton and Lithium Beams

Multicentric investigation of ionising radiation-induced cell death as a predictive parameter of individual radiosensitivity

Identification of genes involved in radiation‐induced G1 arrest

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Identification of genes involved in radiation‐induced G₁ arrest