Assessment of human tumour proliferation using bromodeoxyuridine--current status

The study of human tumour proliferation has been facilitated by the development of monoclonal antibodies recognizing halogenated pyrimidines. Flow cytometry can be used to detect the incorporation of bromodeoxyuridine (BUdR) into DNA simultaneously with the measurement of total DNA content. We have studied in excess of 600 tumours using in vivo administration of BUdR. The cell kinetic information generated from this approach is more complete than can be obtained from in vitro incubation with DNA precursors such as tritiated thymidine (3HTdR) or by single parameter DNA analysis. The duration of S-phase (Ts) can be estimated in addition to the labelling index (LI). From these two parameters, the potential doubling time (Tpot) can be calculated. Our data show a wide variation in Ts as well as LI, making both these parameters important variants in determining overall proliferation. Although there is tremendous variation in Tpot between tumours of the same and different types, the median values are surprisingly short at around 5 days. A close relationship exists between the presence of DNA aneuploidy and the proliferation parameters. The clinical relevance of Tpot is currently being assessed independently in two trials of accelerated versus conventional fractionation.