Effects of administration of basic fibroblast growth factor on hypoxic fractions in xenografted DLD-2 human tumours: 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) to mice bearing xenografted DLD-2 human colon cancers would increase treated tumour growth rates as compared to control neoplasms. Additionally, at the end of the 7 day treatment period, clonogenic excision assays showed that the percentage of hypoxic cells in tumours from mice receiving FGF-2 administration was significantly decreased as compared to control neoplasms (from about 42 to about 19%). The present study was undertaken to better define the kinetics of changes in hypoxic percentages as a function of tumour volume and FGF-2 treatment. In sham-injected 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 postimplantation (respective average volumes 220, 910, and 2810 mm3). In contrast, 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 FGF-2 treatment schedule, but for at least 1 week after the cessation of growth factor administration. The hypoxic percentage was 16% on day 29 postimplantation, even though average tumour volumes were about 4325 mm3. These data show that the effect of FGF-2 administration on tumour growth rate and hypoxic percentages in xenografted DLD-2 neoplasms is rapid, and continues for some period of time even after administration is ended. Studies of tumour perfusion with injected 86RbCl at equivalent tumour volumes of about 1800 mm3 indicated that the percentage of cardiac output to FGF-2 treated tumours was 33% greater than in sham-injected control neoplasms.