New Approaches to the Measurement of Proliferation Rates

Abstract

The field of cell proliferation kinetics has expanded enormously since the original description in 1953 that DNA synthesis in preparation for the next mitosis occupies a discrete portion of the intermitotic life cycle. Howard & Pelc (1953) defined the phases of the cell cycle, i.e. the postmitotic gap (G1), DNA synthesis (S) and the premitotic gap (G2). This nomenclature has become very commonly adopted. Specific precursors of DNA have been developed which allow cells in this phase of DNA synthesis to be labelled. The most extensively used has been radioactive tritiated thymidine, but this is now being replaced by the non-radioactive halogenated pyrimidines BUdR and IUdR. The radioactive precursors were detected in autoradiographs by the grains they induce in a photographic emulsion as the isotope decays. The overall uptake can also be detected in a scintillation counter. By contrast the BUdR or IUdR labelled cells can be detected with specific monoclonal antibodies, which can then be tagged with coloured or fluorescent stains and identified in histological sections or by flow cytometry (Gray et al. 1986).