VARIATION OF GROWTH-RATE OF A RAT-TUMOR DURING A LIGHT-DARK CYCLE - CORRELATION WITH CIRCADIAN FLUCTUATIONS IN TUMOR BLOOD-FLOW

To determine whether tumour growth is influenced by circadian variations in tumour tissue blood flow, we measured changes in area doubling time of tumours (Sate lung carcinoma) within transparent chambers and changes in tissue blood flow of rat subcutaneous tumour during a light-dark cycle. Rats were subjected to an artificial light-dark cycle with light from 7 a.m. to 7 p.m. Tumour doubling times (TDTs) during the dark and the light spans were 33.5 +/- 11.9 h (n = 38, 20 rats) and 70.6 +/- 36.9 h (n = 39, 20 rats) respectively. The former was significantly shorter than the latter (P <0.001). In addition, the larger the tumour became, the longer was the TDT during the light span (P <0.05). Tumour tissue blood flow during the night (10 p.m.-4 a.m.) was approximately 1.5 times greater than that during the day (10 a.m.-4 p.m.). The time during which tumours actively grow and that during which tissue blood flow in tumours increases coincided. These results strongly suggest that tumour tissue blood flow is a determining influence on tumour proliferative activity and that tumour growth is influenced by circadian variations in tumour tissue blood flow.