196 L. A. STOCKEN 



could be divided into discrete periods which they called Gi. S, G2 and D. 



To jiroduce the same inhibition of uptake of DNA precursors several 

 times the dose is required if it is given in S than if the same dose is given 

 in Gi. Similar results have been obtained in regenerating liver l^y Kelly 

 (1957) who used carbon tetrachloride to destroy liver cells and by 

 Holmes and Mee (1956) who surgically removed two-thirds of the liver. 

 Barbara Holmes also showed that if 450 r was given just before partial 

 hepatectomy there was the same inhibition and mitotic delay as when 

 the dose was delivered at 1 2 hr after hepatectomy. 



So far as mitotic delay is concerned one should perhaps remember 

 that Carlson (1948) has shown that an arrest can be caused by as little 

 as 4r and Forssberg and Novak j(1960) that doses of 0-1 r and less 

 affected the growth of Phycomyces BJakeshnnus. 



We have very little infoi-mation about the biochemical events taking 

 place during the j^rocess of division but we now know quite a lot about 

 the biochemistry of interjihase in mammalian cells. During the first 

 part of the cycle there is an early stimulation of RNA and protein syn- 

 thesis. This has been shown both in vivo and in vitro at 6 hr after partial 

 hepatectomy. This is followed by the appearance of thy midy late 

 kinase and DNA polymerase (Bollum et a1., 1960) and the synthesis of 

 DNA does not start until about 15 to 18 hours post hepatectomy. It is 

 also to be noted that at the same time as the synthesizing enzymes appear 

 there is a reduction in the pyrimidine catabolizing enzymes. 



The effect of radiation on these various steps is of some interest. If 

 the irradiation is given before the time at which the enzyme can be 

 detected then its appearance is delayed, but when the enzyme is 

 present the same radiation dose has veiy little effect. In view of the 

 relationship of RNA with protein and enzyme synthesis it is of interest 

 that Welling and Cohen (1960) have observed a decreased incorporation 

 of 32p into nuclear RNA of regenerating rat liver if the animal is 

 irradiated within 6 hr of partial hejmtectomy. There is also a delay in 

 the disap]:)earance of the catabolizing enzymes. Okada and Hempel- 

 mann (1959) have data at 12 hr post-hepatectomy and a more complete 

 time course has been obtained by Stevens in our laboratory (Table I). 

 This delay, of course, only applies in comparatively low doses and when 

 lethal doses are given it is likely that these changes are made irre- 

 versible by more fundamental damage, such as an alteration in the 

 template. 



Cole and Ellis (1954) have observed changes in spleen nucleoprotein 

 after irradiation in vivo and by means of column chromatography we 

 have found changes in thymus DNA (Old and Stocken, 1960). Recently 

 Mrs. Hudnik-Plevnik in our laboratory has also obtained preliminary 



