The Effect of Alterations in Haematocrit on Tumour Sensitivity to X-rays

Abstract

Hypoxic cells in human tumours probably contribute to the failure of radiotherapy in some sites. Changes in the oxygen carrying capacity of the blood, such as in anaemia, have been shown to influence tumour response. The effect of acute and chronic changes in haematocrit on the radiosensitivity of three mouse tumours (EMT6, KHT and RIF-1) were studied. Alterations in haematocrit were achieved by bleeding followed by retransfusion. When radiation was preceded immediately by an acute reduction in haematocrit (anaemia), radiosensitivity was markedly reduced in each tumour. An acute rise in haematocrit (polycythaemia) increased or decreased X-ray sensitivity depending on its severity. The optimum haematocrit for maximum sensitivity was always found to be at a level 5-10 per cent above normal. When the time between induction of anaemia and irradiation was increased, simulating a progressively longer duration of anaemia, marked changes in radiosensitivity of all the tumours were observed. A short duration of anaemia resulted in a resistant tumour with each cell line, but the resistance was gradually lost as the anaemia was prolonged, even though no recovery in haematocrit occurred. The rate of recovery to normal radiosensitivity varied from 24 to 72 hours in the different tumours. Therefore, only haematocrit changes which occurred within 1-3 days of a dose of radiation affect the radiosensitivity of these tumours.

The influence of haemoglobin affinity for oxygen on tumour radiosensitivity

“…obtained in 2 independent experiments. tumour radiosensitivity was mediated through the change in haemoglobin, as the time scale of the events was not entirely consistent and other adaptive processes could have occurred as the tumours experienced a low 02 environment (Siemann et al, 1979;Hirst et al, 1984;Hirst, 1986). The present study aimed to separate the two phenomena: changes in blood biochemistry induced by the breathing of oxygen at lowered tension on the one hand and radiosensitization on the other.…”

Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer

“…Tumor hypoxia results in relative irradiation and chemotherapy resistance. [4][5][6][7] In addition, hypoxia is an important stimulus for angiogenesis; it drives the process of malignant progression resulting in the up regulation of enzymes and proteins which lead to tumor invasion, the down regulation of cell surface antigens resulting in cell detachment, genomic instability with mutagenic properties and the increased clonal selection of cells with apoptosis enhanced survival. 8 It has been assumed that low hemoglobin levels may therefore result in impaired tumor oxygenation, although tumors exposed to low levels of oxygen as seen in the chronic anemia of malignancy are able to adapt to the microenvironment and restore tumor oxygenation.…”

Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia

“…However, the results of these studies are not unanimous, describing an increase in radioresistance (Hewitt et al, 1971;Hill et al, 1972;Hirst et al, 1984;McCormack et al, 1990), no effect on the outcome of radiotherapy (Hirst et al, 1984;Joiner et al, 1993) but also an increase in radiosensitivity (Rojas et al, 1987). One major factor affecting radioresistance during anaemia seems to be the period of time over which anaemia occurred.…”