Circadian rhythms in DNA synthesis are described for the tongue epithelium, five different regions of the alimentary canal (gut)--esophagus, stomach, duodenum, jejunum and rectum--and bone marrow in a group of BDF1 male mice. A circadian rhythm is also described for the mitotic index in the corneal epithelium in the same mice. The data document for the first time in the same animals the dramatic variation in cell division encountered from one region of the gut to another. This variation is seen in the amplitudes of the rhythms as well as in the over-all 24-hour means. On the contrary, the phasings of the rhythms in the different regions of the gut are remarkably similar. In this study, where the mice were standardized to 12 hours of light (0600-1800) alternating with 12 hours of darkness, the peak of the DNA-synthesis rhythm occurred around the time of transition from dark to light, and the trough around the time of transition from light to dark. The implications of these findings, and those of others, to the study of cell kinetics and to cancer chemotherapy are discussed.

Mice (BDF(1)) inoculated with L1210 leukemia survive for a statistically significantly longer span when four courses of arabinosyl cytosine are administered at 4-day intervals-not in courses consisting of eight equal doses at 3-hour intervals, but in sinusoidally increasing and decreasing 24-hour courses, the largest amount being given at previously mapped circadian and circannual times of peak host resistance to the drug. This finding relates to the many therapeutic situations involving rhythmic, and thus predictable, cycles in the host's tolerance of undesired effects from the agent used.

No abstract

With other environmental factors rigidly standardized, normal SpragueDawley rats were maintained under the following lighting schedules: (1) LD 12:12, artificial light from 6:OO A.M. to 6:OO P.M. alternating with 12 hours of darkness; (2) DL 12:12, reversal of the first schedule; (3) DD, constant darkness; and ( 4 ) LL. constant illumination.During each lighting regimen, blood glucose levels were determined on separate subgroups of 11 to 18 animals at bi-hourly intervals during a 24-hour period. Significant circadian fluctuations or rhythms under all lighting conditions were found when the mean blood glucose values for each bi-hourly group were plotted as a function of time. Rats maintained under LD 12:12 conditions showed approximately a 25% difference between the maximum and minimum values. When the phasing of the peaks and troughs of blood glucose rhythm in Sprague-Dawley rats was compared with that of a separate colony of Wistar rats, it was noted that they wgre similar. Starvation of the LD rats for 66 hours did not abolish the characteristic rhythm, although a lower level of blood glucose resulted. The LD 12:12 blood glucose pattern was reversed by reversing the LD cycle 180 degrees. Under LL and DD the troughs and crests seen in the glucose curves were out of phase with those of LD and with each other; this suggested that under LL or DD the rhythm had become free-running because of the absence of the light-dark synchronizer.Hypophysectomy modified the phasing of the normal LD pattern but did not abolish its fluctuating nature; this suggested that the LD cycle of light no longer was an effective entraining agent. Adrenal medullectomy caused an overall 13% decrease in the 24-hour mean but did not alter the phasing of the LD pattern.The significance of periodicity analysis in relation to bioassay is discussed.