874 ADVENTURES IN RADIOISOTOPE RESEARCH 



Comment on paper 88 



In paper SS it is emphasized that in most cases the radiosensitivity of an organ 

 is proportional to its DNA turnover. Ah-eady half a century ago Bergonie and 

 Tribondeau observed a connection between the radiosensitivity of an organ and 

 its mitotic figure. As mitosis is preceded by DNA formation, a connection as the 

 above mentioned one has to follow from Bergonie and Tribondeau's consideration. 

 The measurement of the rate of formation of labelled DNA will often be preferred 

 to the counting of mitoses. 



DNA turnover indicates mostly cell turnover. If the latter is rapid, as in the 

 case of bone marrow, for example, little time will be at disposal to replace the 

 destroyed cells and we shall find the organ to be radiosensitive. In the resting liver 

 cells, dying per day make out less than 1/100 of those dying in the bone marrow. 

 Replacement is correspondingly less exacting in the resting liver than in the bone 

 marrow and the radiosensitivity of the liver lags much behind that of the bone 

 marrow. 



The radiosensitivity of the liver cell has not necessarily to differ from that of 

 the marrow cell. The rapidly growing liver with its high DNA turnover rate is 

 radiosensitive. We found in paper 72 the turnover rate of the liver of a 4 days 

 old rat to amount to 40 times that of the fully grown animal. 



Non-dividing lymphocytes are the most conspicuous example in which radio- 

 sensitivity is not going hand in hand with a high DNA turnover. Ord and Stocken 

 oonsider it proVmVjle that the difference between dividing cells and lymphocytes 

 may be attributed to the part which the cytoplasma, and particularly the mito- 

 chondria, can play in restoring or by- passing damage to the nucleus. In a dividing 

 cell the nuclear damage can prevent multiplication and, if large exposures are used, 

 disturbances in the mitochondria can prevent any reversal of the nuclear disorders, 

 although with smaller exposures mitochondrial alterations are slight. In the non- 

 dividing lymphocyte the volume of cytoplasm and number of mitochondria are 

 very small. Nuclear metabolism is therefore a major factor in the economy of the 

 <;ell, and its inhibition can have serious consequences because of the inability of 

 the cytoplasm to overcome the damage. 



The work of Howard and Pelc on bean-root tips and of Lajtha and his collea- 

 gues with human bone marrow cultures had indicated that synthesis of DNA 

 occurs during a limited period of the mitotic cycle. Irradiation with ionizing radia- 

 tion even after this period, which in bone cells amounts to 12 hours, is terminated 

 and the full DNA complement reached, may stop the mitotic process. The depres- 

 sion of DNA synthesis following exposure to ionizing radiation does not necessarily 

 indicate a radiosensitivity of the DNA formation but may be due to an indirect 

 effect of the above types. The conclusion, however, occasionally met that the effect 

 of irradiation on DNA formation is always due to such an indirect effect can hardly 

 be maintained. Lajtha and associates studied the dose responce curve of X-rays 

 on synthesis of DNA in human marrow bone cells and also on the mouse Ehrlich 

 ascites tumour cells during a 4 -hour incubation period during which all the cells 

 investigated were in their period of synthesis of DNA. Their experiments brought 

 out that up to 414 hours after a dose of 2000 rads synthesis of DNA is not stopped 

 but produced at a reduced rate, thus less labelled desoxyribose nucleic acid is 

 <'o!lected per cell during unit time. The decreased rate synthesis does not become 



