ELIMINATION OF LOW DOSE HYPER-RADIOSENSITIVITY IN T-47D CELLS : The significance of dose-rate and oxygen level

Abstract

Like the majority of investigated cell lines, T-47D breast cancer cells display a pronounced low dose hyper-radiosensitivity when irradiated with 60Co ƒ×-rays. The well-known transient abolition of hypersensitivity by a pre-exposure (priming) of 0.3 Gy given at a high dose-rate of 40 Gy/h was confirmed in the present work. Furthermore, it was discovered that when the dose-rate of the priming dose was lowered to 0.3 Gy/h, the hypersensitivity of the primed cells was persistently eliminated. In experiments, where medium was transferred from irradiated cells to unirradiated cells, it was found that medium from low dose-rate primed (but not high dose-rate primed) cells removed hypersensitivity in the recipient cells suggesting the presence of an active factor in the medium. The recipient cells recovered their hypersensitivity within two weeks indicating that only the cells that are directly irradiated at the low dose-rate produce the factor. Surprisingly, the factor could also be induced in medium that was harvested from unirradiated cells and given the low dose-rate irradiation without cells present and it was shown that a constituent of the serum of the medium was involved in the process. On the basis of the experiments with low dose-rate priming, a model to explain the mechanisms of the observed effects was proposed. Low oxygen levels (hypoxia) are known to affect the radiosensitivity of cells. In the present work T-47D cells were observed to lose their hypersensitivity when grown with 4% oxygen in the gas-phase. However, the hypersensitivity returned within two weeks of reoxygenation. It was also shown that medium transferred from the hypoxic cells to un-treated cells removed hypersensitivity in the recipient cells. Hence, there appear to be many similarities between the effect of medium transfer from low dose-rate irradiated cells and of chronic moderate hypoxia, and it was speculated whether it could be the same factor responsible in the two cases.