Repopulation characteristics and cell kinetic parameters resulting from multi-fraction irradiation of xenograft tumors in SCID mice

Abstract

Purpose: Cell kinetics and repopulation rates during multifraction irradiation have previously been measured in SiHa human cervical carcinoma cells grown as spheroids. The current study applied similar techniques to SiHa tumor xenografts with the ultimate goal of assessing the clinical prognostic value of in situ cell kinetics. Methods and Materials: SiHa (human squamous cell cervical tumor) cells were inoculated subcutaneously in the flank or back of SCID mice. When tumors reached a size of 200–300 mg, they received 25 Gy in 10 fractions over 5 days. Tumor regrowth and cell kinetics parameters were followed during treatment, and for 10 days after completion by measuring tumor volume and analyzing cellular BrdUrd and IdUrd incorporation with flow cytometry. Results: Tumor volume was of limited use in assessing response to irradiation. The fraction of proliferating cells increased early during irradiation as did the labeling index; potential doubling time (T pot) decreased during treatment and returned to the pre-irradiation value after treatment. Cell cycle time remained relatively constant throughout the experiments. Conclusion: These results confirm the feasibility of evaluating cell cycle kinetics and repopulation parameters in a murine tumor model undergoing a fractionated course of irradiation. Repopulation of clonogenic tumor cells occurred more rapidly than predicted by pretreatment measurements, primarily due to an increased growth fraction and consequent decrease in T pot.