Cell production rates in human tissues and tumours and their significance. Part II: clinical data.

This paper reviews the available data for cell production rates of human tissues and tumours, measured in vivo using halogenated pyrimidine labelling and laser cytometry. The technique has now been widely evaluated, and we draw general inferences from the proliferative data over a broad range of tumour and tissue types. Estimates of the S-phase duration, the time taken for DNA synthesis in cycling cells, are consistent over a narrow range with a median value of around 10 hours, notwithstanding the constraints of the experimental and statistical technique, in normal tissues and tumours. This suggests that Ts values may be a species-specific constant. The more easily measured labelled S-phase fraction, or labelling index, shows much greater intra and intertumour variation within any one tumour class. It may thus be a surrogate for time dependent measurements to a first order approximation. The cell production rate, described by the potential doubling time (Tpot), is remarkably rapid in most tumours, a median value of the order of 5 days, and much faster than clinical volume doubling times for most lesions. The rapid cell production rates in normal tissues and tumours highlight the importance of cell loss in the growth and modelling of biological structures. Cell production rate measurements do not adequately describe the biological aggressiveness of tumours. They may be used to refine adjuvant strategies for radiotherapy and chemotherapy in experimental research. Dynamic halogenated pyrimidine labelling has provided unique and valuable insights into the living biology of human tissues and tumours.