Tumor repopulation during radiotherapy: quantitation in two xenografted human tumors

Purpose: 'Accelerated repopulation' has generated considerable recent interest. Our purpose in this study was to determine whether flow cytometry measurements like those used for classical Tpot determinations could be used to quantify the rate of repopulation, and the time of its initiation in irradiated human tumor xenografts. Methods and Materials: Two human tumor cell lines (SiHa, a squamous cell cervix carcinoma, and WiDr, an adenocarcinoma of the colon) were grown as subcutaneous xenografts in SCID mice. Tpot was measured in a conventional manner using flow cytometry, for control tumors and for tumors exposed to five fractions of 4 Gy twice daily over a 2-day interval. For the irradiated tumors, Tpot measurements were conducted 48 h following the final exposure. Results: Active proliferation even after irradiation was observed in both the radiosensitive SiHa and more radioresistant WiDr tumors, and the estimated repopulation rate was at least as fast as would have been predicted by the pre-treatment Tpot estimates. Conclusions: Our data clearly indicate tumor cell proliferation after only a few fractions of radiation exposure in these human tumor xenografts. Additionally, the data suggest that pretreatment Tpot values may underestimate the actual regrowth rate