Individual Radiosensitivity Does not Correlate with Radiation-Induced Apoptosis in Lymphoblastoid Cell Lines or CD3+ Lymphocytes

Wistop, A.; Keller, Ulrike; Sprung, Carl N.; Grabenbauer, Gerhard G.; Sauer, Rolf; Distel, Luitpold

doi:10.1007/s00066-005-1372-0

Cited by 20 publications

(14 citation statements)

References 39 publications

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“…A decrease in levels of radiation induced apoptosis with increasing age was reported in studies investigating CD3, CD4 and CD8 lymphocytes (Wistop et al, 2005;Ozsahin et al 1997). The data from these studies agreed with the data found in this study.…”

Section: Discussionsupporting

confidence: 91%

Individual Radiosensitivity and its Relevance to Health Physics

et al. 2007

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ᮀ Radiation protection regulations have been established to reduce exposure of individuals to acceptable safe levels. These limits assume that people have similar responses to ionizing radiation and that there is no variation in individual radiation risk. The purpose of this research was to determine if apoptosis in lymphocytes can be used to assess individual sensitivity to ionizing radiation. Blood samples were taken from 54 males ranging in age from 19-85 years. Apoptosis was measured using modified flow cytometry based Annexin-FITC/7AAD and DiOC 6 /7AAD assays in different populations of lymphocytes (total mixed lymphocyte population, subset CD4+ or CD8+ lymphocytes) after exposure to in vitro doses of 0, 2, 4 or 8Gy (dose rate 0.1Gy/min). The variation in individual responses to radiation was large. The variation was the largest in the CD4+ lymphocyte subpopulation. Radiation-induced apoptosis decreased with age of donor demonstrating that as people age their lymphocytes may become relatively more resistant to radiation. This research shows that individuals have marked differences in their sensitivity to radiation and protection policies may someday need to be tailored for some individuals.

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Section: Discussionsupporting

confidence: 91%

Individual Radiosensitivity and its Relevance to Health Physics

et al. 2007

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“…Loss of clonogenicity could be due to differentiation, senescence, and, predominantly in lymphocytes and lymphoblastoid cell lines, the induction of apoptosis [38]. Probably, diverse events lead to the reduced amounts of cells in G2/M.…”

Section: Discussionmentioning

confidence: 99%

“…When the G0 assay is used, the observed chromosomal aberrations are the consequence of either insufficient DNA repair [5,24,30,31,33], aberrant signal transduction for cell-cycle control, inappropriate activation of cell death as through apoptosis, differentiation, or senescence [29,35,38]. One major mechanism which prevents cells to undergo permanent DNA damage is the induction of a cell-cycle arrest, giving cells time to repair DNA damage and to avoid an unintentional progression through the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Potential for the G2/M Arrest Assay to Predict Patient Susceptibility to Severe Reactions Following Radiotherapy

et al. 2007

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The interrelation between G2/M arrest and radiosensitivity is not readily apparent since a variety of radiosensitive cells from patients with radiosensitive syndromes and patients identified as radiosensitive following radiation treatment showed inconsistent G2/M arrest dynamics. Secondary effects, like loss of clonogenicity, G1/S phase arrest and failure of G2/M arrest may contribute to variation of the G2/M arrest endpoint and obscure assessment of cellular radiosensitivity using this method.

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“…After up to 72 h of incubation in standard conditions, the cells were fixed for 15 min in 4% paraformaldehyde and visualized using a fluorescence-microscope (Zeiss, Axioplan, Oberkochen, Germany) with a suitable filter combination (Fluorescein/Texas Red) at a 600x magnification. The data was analyzed with the Biomas image analyzing software (Erlangen, Germany) [18]. The values are given as grey values per nucleus [10,11,19,20] after incubation with DOX and DOX-TRF.…”

Section: Fluorescence Measurements Of the Free Drug And Dox-trf Distrmentioning

confidence: 99%

“…At least 1,000 cells per slide were counted blind with a fluorescence-microscope (Zeiss, Axioplan, Oberkochen, Germany) with a suitable filter combination (Fluorescein/Texas Red) at a 400x magnification. The data was analyzed with Biomas (Erlangen, Germany) [18]. The results are given as percentages (apoptotic cells/total cells x 100).…”

Section: Fluorescence Measurements Of the Free Drug And Dox-trf Distrmentioning

confidence: 99%

Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells

Łubgan

Jóźwiak

Grabenbauer

et al. 2009

Cellular and Molecular Biology Letters

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Neoplastic cells frequently have an increased number of transferrin receptors. Coupling transferrin to an anti-neoplastic drug has the potential to overcome multidrug resistance (MDR). The purpose of this study was to examine the distribution and action of doxorubicin-transferrin conjugate (DOX-TRF) in a leukaemia cell line (HL60), a multidrug-resistant leukaemia cell line (HL60ADR) and a normal tissue cell line (human fibroblasts). The intracellular accumulation of DOX and DOX-TRF was monitored by direct fluorescence. More DOX-TRF than free DOX was delivered to the tumour cells, and consecutively the levels of DNA double-strand breaks and apoptosis increased even in the multidrug-resistant cell line. In the normal tissue cell line, DOX-TRF did not accumulate, and therefore, the levels of DNA double-strand breaks and apoptosis did not increase. Cell viability was determined using the MTT assay. The IC 50 for DOX-TRF was lower than the IC 50 value for the free drug in both leukaemia cell lines. The IC 50 values for the HL60 cells were 0.08 µM for DOX and 0.02 µM for DOX-TRF. The IC 50 values for HL60ADR cells were 7 µM for DOX and 0.035 µM for DOX-TRF. In conclusion, DOX-TRF was able to overcome MDR in the leukaemia cell lines while having only a very limited effect on normal tissue cells.

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Individual Radiosensitivity Does not Correlate with Radiation-Induced Apoptosis in Lymphoblastoid Cell Lines or CD3+ Lymphocytes

Cited by 20 publications

References 39 publications

Individual Radiosensitivity and its Relevance to Health Physics

Individual Radiosensitivity and its Relevance to Health Physics

Potential for the G2/M Arrest Assay to Predict Patient Susceptibility to Severe Reactions Following Radiotherapy

Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells

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