CELL-KINETICS AND REPOPULATION MECHANISMS DURING MULTIFRACTION IRRADIATION OF SPHEROIDS

Background and purpose: The objective of the present study was to eval uate the predictive potential of cell kinetic parameters and repopulat ion rates determined by flow cytometry during multifraction irradiatio n of spheroids, a system in which the fate of all cells can be determi ned with high precision. Ultimately, similar analytical techniques sho uld provide a reproducible and prognostically significant clinical pre dictive assay. Materials and methods: Multicellular spheroids of Chine se hamster V79 lung cells were irradiated with 2.5 Gy of 250 kVp X-ray s twice daily to a total dose of 25 Gy. Repopulation parameters and ce ll kinetic parameters were followed throughout the irradiation period and for 5 days after completion of exposure. Results: (1) Regrowth (RG ) took place early during multifraction irradiation. (2) Potential dou bling time (T-pot) decreased steadily from the early part of treatment , remaining of short duration until the spheroids almost attained the pre-treatment number of clonogenic cells. (3) Accelerated repopulation was mainly due to a decreased cell loss factor (Phi) and increased gr owth fraction (GF), although a modest decrease in cell cycle time (t(c )) was suggested. (4) Phi decreased during exponential RG. (5) Other p arameters such as observed doubling time (t(d)) and labelling index (L I) paralleled these findings. Conclusions: Clonogen repopulation that began early in the irradiation scheme and accelerated rapidly is not c onsistent with the prevailing view that accelerated repopulation begin s several weeks into clinical protocols. Also, pre-treatment T-pot did not adequately estimate the repopulation speed in the spheroids. Equi valent studies in animal tumour systems, and then in the clinic, are c onsequently indicated and of some urgency. (C) 1998 Elsevier Science I reland Ltd.