EFFECTS OF ADMINISTRATION OF BASIC FIBROBLAST GROWTH-FACTOR ON HYPOXIC FRACTIONS IN XENOGRAFTED DLD-2 HUMAN TUMORS - TIME-DEPENDENCE

A previous publication (Leith et al., 1992) showed that administration of basic fibroblast growth factor (FGF-2, 0.25 mg kg-1, q.i.d. x 7) t o mice bearing xenografted DLD-2 human colon cancers would increase tr eated tumour growth rates as compared to control neoplasms. Additional ly, at the end of the 7 day treatment period, clonogenic excision assa ys showed that the percentage of hypoxic cells in tumours from mice re ceiving FGF-2 administration was significantly decreased as compared t o control neoplasms (from about 42 to about 19%). The present study wa s undertaken to better define the kinetics of changes in hypoxic perce ntages as a function of tumour volume and FGF-2 treatment. In sham-inj ected control tumours, the hypoxic percentage increased from about 14% at day 15 postimplantation, (i.e. when sham- or FGF-2 injections were begun) to about 42% by day 22, and to about 75% at 29 days postimplan tation (respective average volumes 220, 910, and 2810 mm3). In contras t, the hypoxic percentages in mice treated with FGF-2 remained at the levels seen in control mice on day 15, not only throughout the 7 day F GF-2 treatment schedule, but for at least 1 week after the cessation o f growth factor administration. The hypoxic percentage was 16% on day 29 postimplantation, even though everage tumour volumes were about 432 5 mm3. These data show that the effect of FGF-2 administration on tumo ur growth rate and hypoxic percentages in xenografted DLD-2 neoplasms is rapid, and continues for some period of time even after administrat ion is ended. Studies of tumour perfusion with injected (RbCl)-Rb-86 a t equivalent tumour volumes of about 1800 mm3 indicated that the perce ntage of cardiac output to FGF-2 treated tumours was 33% greater than in sham-injected control neoplasms.