PURPOSE: Do tumor cells which survive high dose fractionated irradiation exhibit modified metastasis activity, proliferation kinetics, and/or radiation sensitivity? To address this question experimentally, we have studied three recurrent human tumor xenograft systems. METHODS AND MATERIALS: Three models were derived from a soft tissue sarcoma (HSTS26T), a colon adenocarcinoma (HCT15), and a glioblastoma (HGL21) which had recurred after 90 Gy, 109 Gy, or 77.4 Gy administered in 30 equal doses, respectively. Their production of spontaneous metastasis and cell proliferation characteristics were studied in early generation xenografts in SCID mice, and were compared to those in their previously unirradiated counterparts. As a control, we have also studied each tumor as a post-surgical recurrence. Specimens from the irradiated recurrent and their unirradiated primary tumors were cultured in vitro and their radiation sensitivity determined by clonogenic assay. RESULTS: The three irradiated recurrent tumor systems retained the individual histological features of their unirradiated primary xenografts. A lower metastatic incidence was observed in two of the three irradiated recurrent tumor lines in comparison with their unirradiated control tumors and their surgical recurrent counterparts. No significant differences were found between the irradiated recurrent tumors and their unirradiated counterparts with respect to: volume doubling time, growth time, potential doubling time, mitotic index, PCNA index, and SF2 values. CONCLUSIONS: High dose irradiation given in 30 fractions did not increase the metastatic activity in the three human tumor xenograft systems. Furthermore, the fractionated irradiation did not significantly change their proliferation characteristics and cellular radiation sensitivity.
PURPOSE: Do tumor cells which survive high dose fractionated irradiation exhibit modified metastasis activity, proliferation kinetics, and/or radiation sensitivity? To address this question experimentally, we have studied three recurrent humantumor xenograft systems. METHODS AND MATERIALS: Three models were derived from a soft tissue sarcoma (HSTS26T), a colon adenocarcinoma (HCT15), and a glioblastoma (HGL21) which had recurred after 90 Gy, 109 Gy, or 77.4 Gy administered in 30 equal doses, respectively. Their production of spontaneous metastasis and cell proliferation characteristics were studied in early generation xenografts in SCIDmice, and were compared to those in their previously unirradiated counterparts. As a control, we have also studied each tumor as a post-surgical recurrence. Specimens from the irradiated recurrent and their unirradiated primary tumors were cultured in vitro and their radiation sensitivity determined by clonogenic assay. RESULTS: The three irradiated recurrent tumor systems retained the individual histological features of their unirradiated primary xenografts. A lower metastatic incidence was observed in two of the three irradiated recurrent tumor lines in comparison with their unirradiated control tumors and their surgical recurrent counterparts. No significant differences were found between the irradiated recurrent tumors and their unirradiated counterparts with respect to: volume doubling time, growth time, potential doubling time, mitotic index, PCNA index, and SF2 values. CONCLUSIONS: High dose irradiation given in 30 fractions did not increase the metastatic activity in the three humantumor xenograft systems. Furthermore, the fractionated irradiation did not significantly change their proliferation characteristics and cellular radiation sensitivity.