Isotransplants of murine fibrosarcoma (KHT) cells were inoculated i.m. into the hind limbs of 6-8 week-old female C3H/HeJ mice. Intratumoral injection of FGF1 or VEGF proteins decreased hypoxic marker uptake in murine fibrosarcoma KHT. Reduction of tumor hypoxia did not correlate with mRNA expression of transcription factors in tumors. Likewise, there was no significant alteration in either apoptotic frequency or the mRNA levels of 10 apoptotic-related molecules in FGF1- or VEGF-treated tumors. mRNA expression for MCP-1, IL-1 beta, IL-18, and IL-1Ra, however, were decreased in the tumors following FGF1 or VEGF treatment. Among the normal tissues tested (brain, kidney, liver, spleen, and lung), basal mRNA levels for cytokines and chemokines varied. Intratumoral injection of FGF1 or VEGF (6 daily intra-tumor injections of 6 micrograms/mouse) did not alter most cytokine or chemokine mRNA expression in spleen and lung. In summary, alteration of tumor oxygenation by local administration of angiogenic growth factors may be mediated by cytokine/chemokine production in the tumor.
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