The Concentration of Oxygen Dissolved in Tissues at the Time of Irradiation as a Factor in Radiotherapy

Gray, L. H.; Conger, Alan D.; Ebert, M.; Hornsey, Shirley; Scott, O. C. A.

doi:10.1259/0007-1285-26-312-638

Cited by 1,929 publications

(915 citation statements)

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“…Measurements of potential doubling time (Tpot) are currently being undertaken in a series of trials comparing conventional with accelerated fractionation, and some show good evidence that pretreatment cell kinetics can predict treatment outcome (Wilson et al, 1988;Begg et al, 1992; Corvo et al, 1995). The degree of hypoxia within a solid tumour is important as hypoxic cells will be up to three times more resistant to radiotherapy than their better oxygenated counterparts (Gray et al, 1953). Meta-analysis of hypoxia-directed treatments has shown that regimens counteracting hypoxia in tumours are beneficial to patient survival, particularly in head and neck cancer (Overgaard, 1992).…”

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Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo

Webster

Hodgkiss²,

Wilson³

1998

Br J Cancer

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Summary Hypoxia was assessed in three murine tumour models in vivo by measuring the incorporation of 7-(4'-(2-nitroimidazole-1-yl)-butyl)-theophylline (NITP), an immunologically identifiable hypoxia marker that binds bioreductively to cells under low-oxygen conditions. Proliferating cells were labelled in the same tumours by administering the thymidine analogue bromodeoxyuridine (BrdUrd). The relative hypoxia in each cell cycle phase of cells isolated from tumours was assessed by addition of propidium iodide with analysis by flow cytometry. There was no relationship between tumour volume and hypoxia in either the anaplastic sarcoma SaF or the poorly differentiated carcinoma CaNT and only a slight negative correlation in moderately well-differentiated carcinoma Rh. The G1/Go phase contained the greatest number of aneuploid hypoxic cells (aneuploid hypoxia ranging from less than 1% up to 40%, 38% and 71% in SaF, CaNT and Rh respectively), although there were significant amounts of hypoxia present in S-and G/M phases for all three tumours examined. However, the highest proportion of hypoxia occurred in the G/M phase, in which up to 60% of the cells were hypoxic. Simultaneous measurement of hypoxia, proliferation and DNA content using a novel triple-staining flow cytometry method showed that hypoxic cells could actively participate in the cell cycle. In addition, the cell cycle distribution of NITP and BrdUrd labelling showed that hypoxic cells could progress through the cell cycle, although their rate of progression was slower than that of better oxygenated cells.

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confidence: 99%

Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo

Webster

Hodgkiss²,

Wilson³

1998

Br J Cancer

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“…Our experiments with the solid tumours were instigated by our understanding of the rationale for use of OHP-breathing during radiotherapy, as originally proposed by Gray, Conger, Ebert, Hornsey and Scott (1953). This is, that the anoxic cells in solid tumours are situated at the extremity of oxygen gradients and can be oxygenated by extension of such gradients.…”

Section: Discussionmentioning

confidence: 99%

Effect of Induced Host Anaemia on the Viability and Radiosensitivity of Murine Malignant Cells in vivo

Hewitt¹,

Blake²

1971

Br J Cancer

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SUMMARY.-Within 48 hours of the institution of severe phenylhydrazineinduced anaemia in mice bearing ascites tumours or generalised leukaemia, a substantial proportion of the malignant cells disappeared respectively from the peritoneal cavity or infiltrated liver. The results of radiobiological experiments permitting determination of the proportion of viable leukaemia cells which were severely hypoxic and relatively radioresistant in the livers of leukaemic mice, showed that induction of anaemia was associated with a several hundredfold increase in the proportion of such cells. The proportion of hypoxic cells was greatly reduced when the anaemic leukaemic mice were transfused with packed erythrocytes or allowed to breathe oxygen under high pressure. Similar experiments with solid sarcomas indicated that a high proportion of the tumour cells were hypoxic in non-anaemic mice breathing air. The hypoxic fraction was not significantly reduced when tumour-bearing mice were made severely anaemic during growth of the tumour and were later transfused. Thus, the hypoxic cells in leukaemic livers and those in solid tumours are markedly different in their capacity for oxygenation following the induction of relative hyperoxaemia.IT is well known that anaemia is a common complication of human cancer and that a wide variety of factors are implicated in its pathogenesis. In cases in which obvious factors, such as haemorrhage or bone marrow replacement, can be excluded, it is probable that continuous extravasation of blood into the tumour itself is paramount. This process has been demonstrated in several transplanted animal tumours using radio-labelled erythrocytes (Greenfield, Godfrey and Price, 1958). Clinical awareness of the frequency of haematological deficiency, even in cases in which the tumour is quite small in relation to body weight, leads to rectification of anaemia before measures to control the tumour are undertaken.Contrasting with the clinical attentiveness to constitutional depradations associated with localised cancer is the frequent neglect of such considerations in the experimental study of rodent tumours. In our experience, rapidly increasing host anaemia is frequently present when transplanted mouse tumours attain a size at which significant observations of the tumour are likely to be made. For example, terminal depression of tumour growth rate (Laird, 1964) and the microanatomy of extremely large tumours (Inch and McCredie, 1968) have been interpreted without reference to the possible implication of progressive host anaemia in the changes described.

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“…She studied the effect of oxygen on tumor response to irradiation. Hornsey is the co-author of the widely known paper by Hal Gray 14 reporting that oxygen might sensitize a tumor to X-rays more than normal tissues. The authors of the study were the first to suggest the use of oxygen to improve the therapeutic index of radiotherapy.…”

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confidence: 99%

The contribution of women to radiobiology: Marie Curie and beyond

Gasińska

2016

Reports of Practical Oncology & Radiotherapy

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Radiobiology Ionizing radiationTumor radiobiology a b s t r a c t Marie Sklodowska-Curie, an extraordinary woman, a Polish scientist who lived and worked in France, led to the development of nuclear energy and the treatment of cancer. She was the laureate of two Nobel Prizes, the first woman in Europe who obtained the degree of Doctor of Science and opened the way for women to enter fields which had been previously reserved for men only. As a result of her determination and her love of freedom, she has become an icon for many female scientists active in radiation sciences. In 1911, Marie Sklodowska-Curie was awarded her second Nobel Prize for the discovery of radium. Her pioneering work demonstrated that radiation is a powerful tool with a wide range of potential applications, which include a range of diagnostic and therapeutic medical procedures. Marie Curie has left a great deal to the world. Her work led to the development http://dx

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The Concentration of Oxygen Dissolved in Tissues at the Time of Irradiation as a Factor in Radiotherapy

Cited by 1,929 publications

References 5 publications

Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo

Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo

Effect of Induced Host Anaemia on the Viability and Radiosensitivity of Murine Malignant Cells in vivo

The contribution of women to radiobiology: Marie Curie and beyond

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