Altered radiosensitivity in a mouse carcinoma after administration of clofibrate and bezafibrate.
We have investigated the ability of the antilipidaemia drugs clofibrate and bezafibrate, to reduce the binding affinity of haemoglobin for oxygen and to sensitize an experimental tumour (the SCCVII/St carcinoma) in the mouse to radiation. Clofibrate at a high dose (4.1 mmol/kg, p.o.) increased the P50 of the blood by about 10 mm Hg. Its effect on tumour radiosensitivity was dependent on tumour size. Highly significant sensitization, equivalent to a 40-fold reduction in the number of hypoxic cells, was seen in small tumours; but in large tumours there was much less effect. At a low dose, which is close to that currently used clinically (0.3 mmol/kg), clofibrate produced a small and barely significant increase in P50. The effect of low dose clofibrate on tumour radiosensitivity also depended on tumour size, small tumours (200 mg) being significantly sensitized, while no significant effect was seen in large tumours. Bezafibrate, at the low dose of 0.3 mmol/kg, gave a significant increase in P50 (by approximately equal to 8 mm Hg), but sensitization to radiation in small tumours was not impressive and not statistically significant. We must gain a better understanding of the mechanisms involved in these effects before applying this approach to clinical radiotherapy.
Hirst
D G
DG
Department of Radiation Oncology, Stanford Medical School, Stanford University, CA 94305.
Wood
P J
PJ
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002277:Carcinoma / Q000532:radiotherapy*; D002994:Clofibrate / Q000494:pharmacology*; D051379:Mice; D010108:Oxyhemoglobins / Q000378:metabolism; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents
D010108:Oxyhemoglobins; D011838:Radiation-Sensitizing Agents; D002994:Clofibrate; D001629:Bezafibrate