Mitotic Rhythms in Human Cancer, Reevaluated by Electronic Computer Programs—Evidence for Chronopathology2

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Abstract
Specially designed programs for the electronic computer providing useful displays of rhythms for research on cancer were applied to data published earlier by E. Tähti and A. Voutilainen. One such program, the cosinor, detected a statistically significant 24-hour-synchronized circadian rhythm in a set of serial mitotic counts on human mammary cancers but not in squamous or basal cell cancers before or after radiotherapy. Another program, the pooled variance spectrum, applied to the same series of mitotic counts obtained before radiotherapy, revealed that the variance was predominantly in the region of frequencies higher than one cycle in 20 hours, i.e., in the ultradian spectral region. By comparison, the contribution to the total variance from the circadian region, i.e., the contribution from frequencies lower than one cycle in 20 hours (equivalent to periods longer than 20 hours) was smaller. In those series obtained immediately following radiotherapy, analyzed by separate pooled variance spectra, the ultradian variance was reduced. The so-called “relatively-low-frequency quotient” was 30% for the data after radiotherapy and 20% for those before radiotherapy. The immediate response to radiotherapy of the spectrum of mitoses in certain human tumors, while confounded by possible effects of the serial biopsies, probably consisted of a selective reduction of the ultradian variance. The relative predominance of the ultradian variance over the circadian one in certain cancers of mature patients constitutes an aspect of the chronopathology of cancer, with a possible bearing on timing radiotherapy.