Delayed Lethal Effect of X-rays on Fibroblasts Cultivated in vitro.

Studies on the effect of X-rays upon cells growing in vitro have shown that with sufficiently high X-ray doses the outgrowth of the irradiated cell culture can be checked immediately and completely. For colonies of chicken fibroblasts, 250,000 r units are the minimum dose which produces this effect (“the immediate lethal dose”). 1

It is also possible to produce a lethal effect on cells in vitro by exposure to considerably smaller X-ray quantities. X-ray doses, which are themselves too low to cause immediate cessation of growth of the irradiated culture, are capable of exerting a lethal action after a latent period (Fischer and Baastrup, 2 San-tesson, 3 Spear, 4 Cox 5 ). Cultures treated with such X-ray doses continue to grow for some time; but after a certain number of passages, cell growth ceases.

The mechanisms of action of the immediate and the delayed lethal doses, respectively, are, in all probability, fundamentally different. The immediate lethal doses stop the outgrowth in the irradiated culture by altering the motility of the cells. The delayed lethal doses act, on the other hand, by affecting a more susceptible cell function, namely, cell division. Cultures treated with these doses die in the course of subsequent transfers because the cells become incapable of multiplication.

In a previous communication 6 we reported on the delayed effect on cell cultures of X-ray doses of 2,500, 5,000, 12,500, 25,000, and 50,000 r units. It was shown that treatment with 2,500 r units causes a depression in the growth rate of the irradiated culture. This depression is transient and is gradually overcome in the course of subsequent passages. The effect of treatment of cell cultures with doses of from 5,000 r units to 50,000 r units is entirely different. Doses of this magnitude inhibit cell proliferation irreversibly.