The Considerable progress which has been made in the study of cell population kinetics2 in proliferating cell systems has been due primarily to the use of labeled DNA precursors, particularly tritiated thymidine, and the development of high resolution autoradiography (14, 36, 62, 75). These technics have provided elegant methods for kinetic analysis of cellular proliferation which heretofore have been unavailable with the classical methods based on mitotic indices (19, 37, 38, 61). Following administration in vivo, TdR-3H is available to a proliferating cell population for a short interval relative to the duration of DNA synthesis, and all cells synthesizing DNA will incorporate the label (14, 30, 32, 36, 55, 62, 69). Analyses of the quantitative relationships between labeled cells and mitoses and the intervals following injection of TdR-3H provide data which relate to the cell cycle and the cell population and concern: (a) the sites of cellular proliferation; (b) the size of the proliferating populations; (c) the rates of cell division; and (d) the fa tes of cells which emigrate from the proliferative compartment. Quantitative data available for analysis of the kinetics of cellular proliferation in vivo are, by the nature of the experimental procedures used, necessarily restricted almost entirely to small mammals, such as the mouse and the rat (14, 36, 75). The hazards and costs of technics involving multiple sampling procedures and the use of radioactive precursors which are incorporated into the heritable material of the cell have precluded the widespread application of these methods for analysis of cell population kinetics in man, and thus the amount of data available on proliferation rates, growth rates, and control mechanisms in normal and neoplastic human tissues, and particularly solid tissues, is small (1, 3, 4, 9-13, 15, 16, 23, 24, 38, 41-43, 45-49, 67, 69, 71, 77). It is apparent, nevertheless, that the study of the kinetics of normal and tumor cell proliferation is essential for the understanding of clinical malignant disease in man (1, 10, 12, 49, 51). A recent report from this laboratory (24) described preliminary results on a reliable method of in vitro incorporation of TdR-3H in human tissues obtained from surgical and biopsy specimens under conditions in which the incorporation of the label occurs only in those cells which were synthesizing DNA in the patient, thereby providing a pattern of labeling similar to that obtained by in vivo methods. The present study concerns an appraisal of the technic in detail, the experimental method for its standardization, and an evaluation of the quantitative data for assessing the proliferative capacities and growth rates of normal and malignant cell populations.
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Fabrikant et al. (1969) studied this question.