Cell production rates in human tissues and tumours and their significance. Part 1: an introduction to the techniques of measurement and their limitations

In the past two decades, the technology of laser cytometry and use of the halogenated thymidine (HP) analogues bromodeoxyuridine and iododeoxyuridine as proliferation labels, have allowed us to quantify the rate of cell turnover in tissues and tumours, in clinical samples as in laboratory models. The principal studies have used injection of bromo- or iododeoxyuridine to measure cell production rates in vivo. Flow cytometry (FCM) has been used to estimate the S phase labelling index (LI) and the S phase duration (Ts) and calculate the cell production rate, represented by the potential doubling time (Tpot). This has allowed calculation of time-dependent indices of proliferation from single biopsies of HP pulse labelled human tissues and tumours. In the first part of this two-part review, we describe the technique and its limitations as a biological assay. The second part summarizes the knowledge gained about cell production rates and the relevance that this information may have to future investigative, prognostic and treatment strategies.