PERIODICITY IN HUMAN BEINGS AND MICE 825 



(Halberg, 1953, and in press) and the use of a radiotracer and of dif- 

 ferential centrifugation. Moreover, concomitantly, the proportion of 

 cells in mitosis also was determined on slices from the livers used for 

 metabolic work. A two- to threefold decrease in the relative specific 

 activity of DNA ( counts/ min/ jag of DNA P as percentage of counts/ 

 min/iug of acid soluble P) was noted from 08:00 to 24:00 and was 

 followed by a sharp peak at 04:00. The interval between the peak in 

 the RSA of DNA and that of mitosis was --8 hr. This may be con- 

 sidered to be an estimate of the lag period between DNA synthesis 

 and mitosis in intact immature mouse liver (Jardetzky et aL, 1956) 

 and is in accord with the 6- to 12-hr lag period noted at a "lower mag- 

 nification" for regenerating liver (Barnum et aL, 1957). In contrast to 

 DNA, however, RSA of both microsomal and nuclear RNA increased 

 rapidly from 16:00 to 20:00 and then gradually dropped to the lower 

 morning values. These results indicate, first, that the metabolism of 

 nucleic acids as well as mitosis, are 24-hr periodic metabolic functions. 

 Second, that certain aspects of cytoplasmic and nuclear RNA metabo- 

 lism are roughly in phase with each other, and third, that they are dis- 

 sociated in phase from peak DNA metabolism by a lag of ^8 hr. 

 Finally, another lag period of ■^S hr normally exists between DNA 

 synthesis and mitosis in the immature growing liver. 



The relation of peak DNA metabolism to mitosis seems to be of par- 

 ticular interest; the results alluded to above suggest at least certain 

 similarities in the timing of cellular processes, in the mouse (Barnum 

 et aL, 1957; Hornsey and Howard, 1956; Jardetzky et aL, 1956), 

 on the one hand, and in two plant species, bean and hly (Howard and 

 Pelc, 1953; Taylor and McMaster, 1954) on the other. While at the 

 present state of our knowledge such similarities represent only paral- 

 lelisms, they seem to deserve further work, particularly since they are 

 of radiobiologic interest (Howard, 1956). It is pertinent in this con- 

 nection, that the plant studies, as well as work on mouse ascites tumors 

 (Hornsey and Howard, 1956), were done without periodicity analysis. 

 The Minnesota work carried out along the 24-hr scale, however, has 

 already yielded data which may be used for suggesting and sketching 

 — in admittedly crude terms — some chemical stages of a "metabolic 

 clock," at least in one mammalian organ. Rather than speaking of 

 "functional" and "vegetative" states (or of catabolic and anabolic or 



