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H . F I R K E T
but the second division is stopped (Prescott, 1960). W e have already
mentioned the effect of C O poisoning after a certain point, probably
prophase, on sea urchin eggs (Swann, 1954). 200r of y-irradiation on
dividing cells of Viciafaba cause a delay ofthe following division but not
ofthe one in progress (Evans, Neary and Tonkinson, 1959). It is not
easy to demonstrate similar effects in cultures of animals cells, but
perhaps the production at will of one or two waves of division after a
temporary improvement in the nutrient medium of fibroblast cultures
(Jacoby, Trowell and Willmer, 1937) is to be explained by some
chemical storage overlapping on several cycles.
E. E F F E C T OF I O N I Z I N G R A D I A T I O N S ON T H E C E L L C Y C L E
A clear picture of the cell cycle and its phases is essential to the
understanding of the action of the large number of agents, physical and
chemical, promoting or inhibiting cell division. This can be best illustrated by a short survey of the effects of X-rays. The general effect of
X-rays in culture are reviewed in Vol. 3, Chapter 1. W e will here only
mention them in reference to the cell cycle.
The spectacular suppression of mitosis produced by ionizing radiations had been attributed to their inhibition of D N A synthesis. In fact,
as soon as the time sequence of D N A formation was more or less
established, it became clear (Kelly, 1957) that the effect of X-rays preventing, within minutes, cells from entering into mitosis (Perk, 1942)
could not be due to their action on a phenomenon which had already
been completed some hours earlier.
Thus, dosages of 250-500r in cultures act on the extreme end of G 2
without affecting D N A synthesis (Kelly, 1957; Firket, 1958a;
Harrington, 1960; etc.). Tetraploid cells accumulate and this accounts
for the compensatory wave of mitoses observed after the period of
inhibition. Usually more than 500r are necessary to inhibit the S phase.
There is first a slowing down of the D N A formation (Lajtha, Oliver,
Kumatori and Ellis, 1958; Whitfield and Rixon, 1959, etc.) but, only
several thousand r can stop it completely. The duration of the period
without mitoses and the way in which they reappear is the result of a
combination of the two effects, on G 2 and on S.
Sometimes a third effect is observed. In bone marrow, a dose of less
than 300r reduces the number of cells entering into the S period, but
has no effect on those in it, once it has begun (Lajtha et al., 1958). Some
mechanism at the end of G x is thus affected. A similar action may be
responsible for the retardation of incorporation of D N A precursors
during liver regeneration (Holmes, 1956) or the slowing down of
kidney compensatory hypertrophy (Cole and Rosen, 1961) when
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