Summary The proliferative potential of human solid tumours, in vivo, was investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Patients with solid tumours from a variety of sites were injected with 500mg BrdUrd, intravenously, several hours prior to biopsy or surgical excision. The labelling index (LI), duration of S-phase (Ts) and thus the potential doubling time (Tpot) could be measured within 24h of sampling. The results show that both the LI The cellular proliferation of human cancer has been the subject of much study over the years, aimed at rationalising treatment so that schedules more suited to the cell kinetic characteristics of individual tumours can be given. However, progress has been hampered by the nature of the techniques available to measure cell kinetic parameters. The incidence of mitotic figures has been used to relate cell production rate to histological parameters and patient survival (Weiss, 1971). However, this parameter has failed to demonstrate any significant correlation with survival. The stathmokinetic method has been applied to human tumours by several groups (Meyer & Donaldson, 1969;Camplejohn et al., 1973) to overcome the inadequacies of mitotic index alone. However, it is not possible to ensure that maximum mitotic collection rate is achieved. The most widely used method has been to measure the labelling index using tritiated thymidine (3HTdR) and autoradiography. The bulk of the data obtained using this method have come from labelling tumour explants or cell suspensions in vitro (see Steel, 1977; Meyer, 1982 for reviews). Some studies have been performed in vivo (Frindel & Tubiana, 1968;Bennington, 1969;Young & DeVita, 1970;Terz et al., 1971;Bresciani et al., 1974). However, the technique suffers from two major drawbacks. Firstly, the result is not achieved in a time-scale suitable for the clinician to use if treatment is to be based on cell kinetic characteristics. Secondly, its wide use in vivo is precluded due to ethical considerations involved in administering a radioactive precursor of DNA and the requirement for multiple biopsies if cell cycle measurements are to be made.A technique which allows cell kinetic measurements to be made on individual human tumours in a time-scale of use to the clinician in planning the most appropriate treatment, is that based on the flow cytometric measurement of bromodeoxyuridine (BrdUrd) incorporation into DNA (Gratzner, 1982;Dolbeare et al., 1983). We have previously shown that it is possible to measure the labelling index (LI) of human tumours following an in vivo injection of BrdUrd, and using mouse tumours have shown that the BrdUrd technique gives the same information as the use of 3HTdR (Wilson et al., 1985 not radioactive or toxic at the doses required for cell kinetic studies, and it is possible to estimate both the LI and the duration of S-phase (Ts) and hence the potential doubling time (Tpot) from a single biopsy. The technique to estimate Tpot is based on the procedure first described by Begg et ...
