IN-VIVO CHARACTERIZATION BY MEANS OF DIGITAL CELL IMAGE-ANALYSIS OF EARLY-INDUCED FRACTIONATED RADIOTHERAPY EFFECTS ON THE MXT MOUSE MAMMARY-TUMOR

Purpose: To study the cell kinetics and chromatin modifications occurr ing in function of the fractionated irradiation administered to the MX T mouse mammary adenocarcinoma. Methods and Materials: The MXT tumor c ells were submitted to three fractions of a 4.8 Gy dose delivered at 2 4-h intervals. MXT tumor cells were collected by means of fine needle aspirations (between 5 and 10 samples were obtained after each irradia tion) during treatment and submitted to the computer-assisted microsco pe analysis of Feulgen-stained specimens. Three groups of parameters h as been described: i.e., the geometry of the nucleus, the nuclear DNA content, and the chromatin texture. Furthermore, cell cycle parameters were studied in the aim to know the distribution of the cells within the cell cycle. Results: The mean values relating to geometric paramet ers (i.e., the nuclear area and its standard deviation) decreased duri ng treatment. Variations in the nuclear DNA content appeared as being cyclical and could be explained in terms of the modifications in the d istribution of the cells within the cell cycle. The quantitative analy sis of the cell cycle parameters revealed that the percentage of S cel ls increased regularly after each irradiation. In contrast, the percen tage of G(2) cells decreased between each irradiation. The parameters describing nuclear texture showed regular variations between each irra diation. These variations consisted in two cycles constituted by a dec rease in chromatin condensation, followed by an increase. Conclusions: The development of the geometric parameters indicates that fractionat ed radiotherapy leads to the emergence of a more homogeneous populatio n. The effects of the radiotherapy on the distribution of the cells wi thin the cell cycle could be explained through the phenomenon of repop ulation and by the high degree of radiosensitivity of the G(2) cells ( decrease in the percentage of G(2) cells). Last, the variations observ ed at chromatin pattern level could be explained through DNA repair pr ocesses. (C) 1997 Elsevier Science Inc.