Response of Cells of Human Origin, Normal and Malignant, to Acute and Low Dose Rate Irradiation

Dose response curves were obtained for normal human fibroblasts and for several cell lines derived from human tumors, including melanomas and an osteosarcoma. Most of the tumor lines are similar in radiosensitivity to the normal fibroblasts, except for the melanoma lines, which are significantly more resistant. The two melanoma lines differ, one being much more radioresistant than the other. Potentially lethal damage repair (PLDR) has been studied in these cell lines as well. The extent of PLDR does not appear to correlate with radioresistance; for example, the most resistant melanoma line shows very little repair of PLD. In addition, the normal fibroblasts repair PLD at least as well as any of the tumor derived lines, which casts doubts on the wisdom of introducing into clinical practice inhibitors of PLD until a clear differential between normal tissues and tumors has been demonstrated in vivo. Low dose-rate studies with normal human fibroblasts indicate a smaller dose-rate effect than for most established cell lines of rodent origin. Indeed, in the human cells studied, the effect of sublethal damage repair is quantitatively similar to the repair of potentially lethal damage. Dose response curves for acute and protracted exposures have been obtained for cells derived from patients with cancer-prone syndromes including ataxia telangiectasia (AT) and Bloom's syndrome. Both cell lines are much more radiosensitive than normal human fibroblasts; the AT cells show a dose-rate effect, while Bloom's syndrome cells do not.