Radiobiology of a differentiating cell system in vitro.

Friend erythroleukaemia cells (FELC) in vitro were used to examine the effects of ionizing radiation on differentiation and proliferation of mammalian cells. Results suggest that X-rays can affect differentiation in two different ways. First, X-rays inactivate the ability of these cells to respond to an external trigger of differentiation, e.g., dimethyl sulphoxide. Second, X-rays themselves trigger a partial differentiation response, in the absence of any other external trigger. The radiation-induced lesions leading to these two end-points are not repaired in split-dose experiments, unlike those lesions which lead to loss of cell proliferative capacity. The profile of soluble FELC proteins, as analysed by isoelectric focusing, was also affected by irradiation. These effects of ionizing radiation on the expression of genetic information in mammalian cells have important implications for radiobiology, particularly at low doses where acute lethal effects are minimal.

DNA strand breaks, repair, and survival in x-irradiated mammalian cells.

The yields of unrepairable single-and double-strand breaks in the DNA of x-irradiated Chinese hamster cells were measured by low-speed neutral and alkaline sucrose density gradient sedimentation in order to investigate the relation between these lesions and reproductive death. After maximal single-strand remoining, at all doses, the number of residual single-strand breaks was twice the number of residual double-strand breaks. Both double-strand and unrepairable single-strand breaks were proportional to the square of absorbed dose, in the range 10-50 krad. No rejoining of double-strand breaks was observed. These observations suggest that, in mammalian cells, most double-strand breaks are not repairable, while all single-strand breaks are repaired except those that are sufficiently close on complementary strands to constitute double-strand breaks. Comparison with cell survival measurements at much lower doses suggests that loss of reproductive capacity corresponds to induction of approximately one double-strand break.

Kinetics of the single-strand repair mechanism in mammalian cells.

Alkaline sucrose gradient measurements of single-strand breaks from sublethal X-ray doses yield the same breakage efficiency as from lethal doses. Repair of the breaks is random, first order with a single rate constant, and characterized by 24 kcal/mole activation energy.