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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 ...

Bromodeoxyuridine (BrdUrd) incorporation and flow cytometry were used to measure human tumour kinetic parameters in vitro and in vivo. The technique was validated by comparison of labelling index estimates of mouse tumours in vivo and in vitro using BrdUrd and flow cytometry with tritiated thymidine eHdThd) autoradiography. Similar labelling indices were obtained with both in vivo and in vitro incorporation into DNA of the two diffcrcnt precursors. Measurements of human tumour labelling indices were similar following in vitro incubation with either BrdUrd or 'HdThd.The use of BrdUrd allowed the visualization of a population of S-phase cells that did not appear to incorporate BrdUrd or 3HdThd. The human tumour labelling indices obtained with BrdUrd incorporation were similar to previously reported values using autoradiography studies. Preliminary studies demonstrated that significant human tumour labelling could be achieved with an intravenous injection of 500 mg BrdUrd.

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V79 cells have been exposed to X-rays or 238Pu alpha-particles or to X-rays following priming alpha-particle doses of 0.5, 2 or 2.5 Gy. The survival curve for exposure to alpha-particles was exponential with a D0 of 0.89 Gy. Following exposure to priming alpha-particle doses the resulting X-ray survival curves had the same slope as the single dose X-ray curve, but a reduced shoulder. For alpha-particle priming doses of 0.5 and 2 Gy this reduction was the same as for the same X-ray doses. 2.5 Gy alpha-particles reduced the subsequent X-ray curve Dq to almost zero. alpha-particles do cause damage capable of interacting with X-ray damage.