SPONTANEOUS METASTASIS, PROLIFERATION CHARACTERISTICS AND RADIATION SENSITIVITY OF FRACTIONATED-IRRADIATION RECURRENT AND UNIRRADIATED HUMAN XENOGRAFTS

Purpose: Do tumor cells which survive high dose fractionated irradiati on exhibit modified metastasis activity, proliferation kinetics, and/o r radiation sensitivity? To address this question experimentally, we h ave studied three recurrent human tumor xenograft systems. Methods and materials: Three models were derived from a soft tissue sarcoma (HSTS 26T), 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 c ell proliferation characteristics were studied in early generation xen ografts in SCID mice, and were compared to those in their previously u nirradiated counterparts. As a control, we have also studied each tumo r as a post-surgical recurrence. Specimens from the irradiated recurre nt and their unirradiated primary tumors were cultured in vitro and th eir radiation sensitivity determined by clonogenic assay. Results: The three irradiated recurrent tumor systems retained the individual hist ological features of their unirradiated primary xenografts. A lower me tastatic incidence was observed in two of the three irradiated recurre nt tumor lines in comparison with their unirradiated control tumors an d their surgical recurrent counterparts. No significant differences we re found between the irradiated recurrent tumors and their unirradiate d counterparts with respect to: volume doubling time, growth time, pot ential doubling time, mitotic index, PCNA index, and SF, values. Concl usions: High dose irradiation given in 30 fractions did not increase t he metastatic activity in the three human tumor xenograft systems. Fur thermore, the fractionated irradiation did not significantly change th eir proliferation characteristics and cellular radiation sensitivity.