8 p. ALEXANDER AND Z. M. BACQ 



giants with up to thirty times the normal vohnne (Fig. 3). Even after 

 cell division has stopped, DNA and protein synthesis proceed normally 

 for some twelve to fifteen hours. Interference with protein and DNA 

 synthesis only becomes apparent in these cultures some 36 hr after 

 irradiation when the cells can be seen microscopically to be degenerat- 

 ing. 



Cell death under these conditions has frequently been attributed to 

 chromosome damage and undoubtedly the loss of large amounts of 

 genetic material must render a cell non-viable. But this cannot be the 

 only mechanism, for radiosensitivity and chromosome damage do not 

 go hand-in-hand (Oakberg and Minno, 1960; Bender, 1960; Sharman, 

 1959). The possibility must be envisaged that the time interval between 

 irradiation and cell death is needed for the metabolic development of 

 the injury as is the case for all radiation effects. That in rapidly dividing 

 cells mitoses occur during this essential time interval need not imply 

 that mitosis itself is a necessary step for the process of mitotic death ; 

 the mitosis may be coincidental. Evidence for this view is derived from 

 experiments in which cells are prevented from division after irradiation 

 by a treatment that does not suppress metabolism. If the leukaemia cells 

 are kept after irradiation at 22°C for 18 hr and then returned to their 

 normal temperature of 37°C, cell death takes place without intervening 

 mitosis. At the lower temperatures the cells still metabolize although no 

 division occurs (95 per cent of the unirradiated cells survive 18 hr at 

 25°C). 



In this connection it is worth emphasizing that there is no evidence 

 that allows us to link chromosome abnormalities with radiochemical 

 damage to nucleoprotein. The concept that the ionizing particle 

 severs the chromosome or chromotid thread on passing through it finds 

 no support from iw ?;zY/o studies of DNA (Lett et al., 1961a, b) nor does 

 it explain the biological data (Revell, 1959). A time interval is always 

 necessary between irradiation and the appearance of the chromo- 

 some "break". To see a break the cell has to be studied in metaphase 

 or anaphase, yet the irradiation has to l)e carried out hours earlier 

 while the cell is in the resting stage or in early prophase. The explana- 

 tion that the interphase chromosomes are more slender structures 

 that can be severed more easily by an ionizing particle than the visible 

 chromosomes of mitosis is invalid since cells irradiated during mitosis 

 show chromosome "breaks" at a high frequency in the next mitosis. 



RADIOSENSITIVITY, RADIOSENSITIZERS AND INTRACELLULAR 



PROTECTORS 



Many factors are likely to play a part in determining the great 



