Effects of pulses of radiation on the survival of mammalian cells

Nias, A. H. W.; Swallow, A. J.; Keene, J. P.; Hodgson, Brian

doi:10.1259/0007-1285-42-499-553-b

Cited by 46 publications

(24 citation statements)

References 6 publications

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“…21 . Clearly, our data do not support the findings of Nias et al (1973) that sub-lethal damage produced by ultra-high dose-rates is irreparable .…”

Section: Resultscontrasting

confidence: 99%

“…Our observation of the repair of sub-lethal damage for ultra-high dose-rate irradiation is in direct conflict with the findings of Nias et al (1973), and we have no ready explanation for this . One of the main differences in technique is that Nias maintained his HeLa cells in tris-buffered saline plus 10 per cent serum, whereas we used calcium-free MEM supplemented with foetal-calf serum .…”

Section: Discussioncontrasting

confidence: 88%

“…of 0 . 87 for 22 MV X-rays using five different biological systems, and not inconsistent with the findings of Nias et al (1970), who observed relatively large variations in the D o values of aerated HeLa cells when irradiated with X-rays or pulsed electrons, but no consistent pattern to indicate a DMF .…”

Section: Discussionsupporting

confidence: 67%

“…The analysis of cell-survival data indicates that high-energy, pulsed electrons are biologically less effective than 250 kV X-rays . Oxygen consumption does not appear to be responsible for the shift of the pulsed-electron survival curve, as there is no break in the curve (hockey-stick effect) which has been observed when oxygen concentrations fall below critical levels (Epp, Weiss and Santomasso 1968, Nias, Swallow, Keene and Hodgson 1969, Berry and Stedeford 1971 . Our finding of a DMF for 30 MEV pulsed electrons of 0 .…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

The Effects of Ultra-high Dose Rates on Survival and Sublethal Repair in Chinese-hamster Cells

Schulz¹,

Nath²,

Testa³

1978

International Journal of Radiation Biology and Related Studies

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“…21 . Clearly, our data do not support the findings of Nias et al (1973) that sub-lethal damage produced by ultra-high dose-rates is irreparable .…”

Section: Resultscontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 88%

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The Effects of Ultra-high Dose Rates on Survival and Sublethal Repair in Chinese-hamster Cells

Schulz¹,

Nath²,

Testa³

1978

International Journal of Radiation Biology and Related Studies

View full text Add to dashboard Cite

“…For mammalian cellular and chromosomal systems, interesting results were published by several authors between 1967 and 1978. These led to the conclusion that ultra-high dose rates would not necessarily be advantageous and might have adverse consequences because of local oxygen depletion [2][3][4][5][6][7][8][9], with very low oxygen tensions causing significant cellular radioresistance and being capable of reducing local cancer ''cure''.…”

mentioning

confidence: 99%

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Wilson

Jones²,

Yokoi³

et al. 2012

BJR

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Objective: To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy. Methods: A literature search of cellular UHDRR exposures was performed. Standard oxygen diffusion equations were used to estimate the time taken to replace UHDRRrelated oxygen depletion. Dose rates from conventional and novel methods of hadrontherapy accelerators were considered, including spot scanning beam delivery, which intensifies dose rate. Results: The literature findings were that, for X-ray and electron dose rates of around 10 9 Gy s -1 , 5-10 Gy depletes cellular oxygen, significantly changing the radiosensitivity of cells already in low oxygen tension (around 3 mmHg or 0.4 kPa). The time taken to reverse the oxygen depletion of such cells is estimated to be over 20-30 s at distances of over 100 mm from a tumour blood vessel. In this time window, tumours have a higher hypoxic fraction (capable of reducing tumour control), so the next application of radiation within the same fraction should be at a time that exceeds these estimates in the case of scanned beams or with ultra-fast laser-generated particles. Conclusion: This study has potential implications for particle therapy, including lasergenerated particles, where dose rate is greatly increased. Conventional accelerators probably do not achieve the critical UHDRR conditions. However, specific UHDRR oxygen depletion experiments using proton and ion beams are indicated.

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Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH

et al. 2023

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BackgroundUltra‐high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon.PurposeThis work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half‐maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue.MethodsWe developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic‐linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles.ResultsThe results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose‐dependent response trends, if the g value is identical in both tumor and normal tissue.ConclusionsThe therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue‐dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia.

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Effects of pulses of radiation on the survival of mammalian cells

Cited by 46 publications

References 6 publications

The Effects of Ultra-high Dose Rates on Survival and Sublethal Repair in Chinese-hamster Cells

The Effects of Ultra-high Dose Rates on Survival and Sublethal Repair in Chinese-hamster Cells

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH

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