TUMOR-NECROSIS-FACTOR-ALPHA SUPPRESSES THE REGROWTH OF FRACTIONATED IRRADIATED ENDOTHELIAL-CELLS IN-VITRO

Cytokines from two sources may affect endothelial cells (ECs) in tumor therapy: endogenously from cells in tumors and exogenously from thera peutic applications. These cytokines could modulate the influence of o ther therapy on tumor ECs. We use the colorimetric MTT method to asses s the growth of irradiated ECs isolated from bovine pulmonary artery ( CPAEC) and human umbilical cord vein (HUVEC) treated by cytokines. CPA ECs given a single radiation dose of 2.5 to 15 Gy showed a small reduc tion in viable cells 2 to 3 days post-treatment. Neither tumor necrosi s factor-alpha (TNF), interleukin-1 alpha (IL-1), nor interferon-gamma (INF) altered the growth of CPAECs treated by single radiation doses. HUVECs irradiated by a single dose of 12 Gy showed continuous reducti on in viable cell numbers while those treated by 3 fractions of 4 Gy i n 3 days or 6 fractions of 2 Gy in 3 days began to regrow 7 to 8 days after irradiation. Addition of TNF during the fractionated irradiation period limits the regrowth of HUVECs. Addition of IL-1 does not have the same effect. We have also tested the combined effect of another EC active agent flavone acetic acid (FAA), which has also been shown to stimulate the expression of TNF, with radiation. FAA (200 mu g/ml) has a greater inhibitory effect on the growth and regrowth of fractionate dly irradiated HUVECs than TNF. These data suggest that TNF or FAA sho uld be explored along with radiotherapy for their anti-tumor effect.