COMPARISON OF MATHEMATICAL FORMULAS USED FOR ESTIMATION OF DNA-SYNTHESIS TIME OF BROMODEOXYURIDINE-LABELED CELL-POPULATIONS WITH DIFFERENT PROLIFERATIVE CHARACTERISTICS

Growth kinetic data of human tumours, obtained by flow cytometric anal ysis of cells labelled with bromodeoxyuridine (BrdUrd) might provide p rognostic information and allow prediction of response to radio- and c hemotherapy. However, the theoretical models applied for calculation o f growth kinetic data are not fully evaluated. The purpose of this stu dy was to investigate the dependence of the estimation of DNA synthesi s time (T-s) on sampling time after BrdUrd labelling, using four diffe rent mathematical formulas (Begg et al., White & Meistrich, White et a l. and Johansson et al.) which have been developed for the evaluation of flow cytometry-derived data of BrdUrd-labelled cells. In addition, we have investigated the influence of the growth kinetic properties of the cell populations using two cultured cell lines (one slow and one fast growing), and two heterotransplanted human tumours. The dependenc e of the estimation of T-s on sampling time was more or less pronounce d, depending on the cell population examined and on the formula used. In the fast growing cell line, the estimates of T-s did not vary signi ficantly with sampling time when using the formulas by White et al., w hereas in the slow growing cell line, the estimates of T-s did not sho w any significant dependence on sampling time when using the formula b y Johansson et al. In the tumours, the estimation of T-s depended on s ampling time with all formulas used, although to different degrees. In one of the tumours, this was mainly caused by the influence of mouse cells, as we demonstrate. Our results indicate that the proliferative characteristics of a cell population should be taken into consideratio n when choosing a mathematical formula in order to attain T-s values t hat are independent of sampling time.