Influence of Oxygen Tension on X-Ray-Induced Chromosomal Damage in Ehrlich Ascites Tumor Cells Irradiated in Vitro and in Vivo

Deschner, Eleanor E.; Gray, L. H.

doi:10.2307/3570739

Cited by 224 publications

(54 citation statements)

References 8 publications

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“…Similar to what had been shown in plants and insect tissues, Gray found that the ascites tumor cells showed a dependence of radiation sensitivity on O 2 tension both in vitro and in vivo. Sensitivity was about three times greater under well-oxygenated conditions as compared to anoxic conditions 19,20 . Subsequently, Churchill-Davidson published a cytological evaluation of damage in patient tumors after radiation.…”

Section: The Effects Of Hypoxia On Cancermentioning

confidence: 90%

The impact of O2 availability on human cancer

2008

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During the last century, it has been established that regions within solid tumors experience mild to severe oxygen deprivation, due to aberrant vascular function. These hypoxic regions are associated with altered cellular metabolism, as well as increased resistance to radiation and chemotherapy. As discussed in this Timeline, over the past decade, work from many laboratories has elucidated the mechanisms by which hypoxia-inducible factors (HIFs) modulate tumor cell metabolism, angiogenesis, growth, and metastasis. The central role played by intra-tumoral hypoxia and HTF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies.Oxygen (O 2 ) is required for aerobic metabolism to maintain intracellular bioenergetics and serve as an electron acceptor in many organic and inorganic reactions. Hypoxia, defined as reduced O 2 levels, occurs in a variety of pathological conditions, including stroke, tissue ischemia, inflammation, and the growth of solid tumors. The beginnings of hypoxia research in tumor biology can be traced back to observations made in the early 20 th century by Otto Warburg who demonstrated that, unlike normal cells, tumor cells favor glycolysis, independent of cellular oxygenation levels. He postulated that tumor growth is caused by mitochondrial dysfunction in neoplastic cells, forcing them to generate energy through glycolysis (reviewed in 1 ). This hypothesis appears to be incorrect, but a number of other molecular mechanisms promoting "aerobic glycolysis" have been proposed including mutations and epigenetic changes in genes encoding tumor suppressors (e.g. p53), oncogene activation (e.g. c-Myc), and hypoxic adaptations {Denko, 2008 #6606; Gatenby, 2004 #6608; Deberardinis, 2008 #6609.

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Section: The Effects Of Hypoxia On Cancermentioning

confidence: 90%

The impact of O2 availability on human cancer

2008

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“…When theoxygenwas in a gas bubble (method 2), the bubble was introduced into a hydrogen stream through a seal of static oxygen-free water. Convenient techniques have been described by Deschner & Gray (1959) and Dewey & Gray (1961). The stream of hydrogen flowed through a Hersch analyser (Hersch, 1957) where a constant fraction of the oxygen reacted at a moist silver surface to generate a proportionate electric charge.…”

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confidence: 99%

Determination of the oxyhaemoglobin dissociation curves for mouse and rat blood

Gray¹,

Steadman²

1964

The Journal of Physiology

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Schmidt-Nielsen & Larimer (1958) made a comparative study of the oxyhaemoglobin dissociation curves of mammalian blood in relation to body size. Previous to this very few measurements seem ever to have been made of the relation between the oxygen tension and the degree of saturation of the unhaemolysed blood of mice or rats. This is strikingly illustrated by the fact that the figure for the oxygen tension at 50 % saturation quoted by Bartels & Opitz (1958) is taken from Prosser (1950), who in turn quotes from the observations made in 1912 by Douglas, Haldane & Haldane (1912) on blood taken from animals asphyxiated by drowning, which was almost certainly heavily loaded with lactic acid and not characteristic of the animal at rest or in moderate activity. Our object was to compare the oxygen-dissociation characteristics of the blood of the mouse, the rat and man, at identical PCO2 and pH.Two methods of determining the dissociation curves are described below, preceded by reference to the procedures employed for the micro-assay of oxygen and an account of the processes of taking and equilibrating the blood, which are common to both. METHODSTaking and equilibrating the blood The blood was drawn from the heart (in the case of human blood, from a vein in the arm) into a heparinized syringe. That from about a dozen animals was pooled and one drop of 1 % sodium fluoride added for every 3 ml. of blood. The blood was kept on ice until needed. Any adjustment of pH was carried out at this stage. Two millilitres ofthe agitated blood were drawn into a 30 ml. graduated syringe followed by successive amounts of nitrogen, oxygen and carbon dioxide appropriate to the required partial pressures. The PCO2 was approximately 40 mm Hg throughout the experiments (individual values noted in each table). The gas mixture occupied a volume of 28 ml. at room temperature. The needle of the syringe was closed with a short blind length of small-bore rubber tubing, and the syringe rotated for 15 min at 370 C in a water-bath. Care was taken to ensure that the plunger of the syringe was quite free to move inside the barrel, so that the gas was at atmospheric pressure. After 15 min the syringe was removed from the water-bath and the gas expelled. A fresh gas mixture of the same composition was introduced into the syringe and the blood re-equili- After a certain number of measurements had been made on blood drawn from the orbital sinus of anaesthetized mice, it was noted that this blood was invariably acid (pH 7-15) and therefore not comparable with human blood at pH -7-45. In all subsequent work blood was drawn from mice and lightly anaesthetized rats by cardiac puncture. In the case of the mouse blood, the pH of the blood as drawn was often lower than 7-45. In such cases a 2 ml. sample was equilibrated as described below, but for only one period of 10 min, with a mixture of air and carbon dioxide such that the PCO2 was 40 mm Hg. The pH of the blood was measured, and enough N-NaOH added from a microsyringe to the bulk of the blood (on the basis of...

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“…It is with this object in view that rotation beam radiation therapy and other radiation devices have come in vogue. Deschner and Gray (1959) radiosensitivity does not increase with increase in partial pressure of oxygeni. This relationship of radiosensitivity of cells to partial pressure of oxygen is shown in Fig.…”

Section: Knocking Off H20mentioning

confidence: 86%