ROLE OF T-CELLS AND TUMOR-NECROSIS-FACTOR IN ANTITUMOR-ACTIVITY AND TOXICITY OF FLAVONE ACETIC-ACID

To investigate the importance of natural killer (NK) and T cells in the inhibition of tumour growth by flavone acetic acid (FAA), colon 26 murine carcinoma was grafted subcutaneously in euthymic and athymic mice. FAA was active in euthymic but not in athymic mice (ratio between tumour weight in treated vs. control animals [T/C %], 27% and 92%, respectively). NK cell activity was increased in both mouse strains, indicating a lack of major involvement of this lymphocyte population in FAA efficacy. In euthymic mice tumour-specific T cells were activated, and after in vivo depletion of lymphocyte subpopulations (L3T4 and Lyt2), tumour inhibition by FAA was abrogated (T/C %, 88%). Antitumour efficacy of FAA was also reduced when the treatment was followed by injection of antitumour necrosis factor alpha (TNF-alpha) antibodies. FAA toxicity depended on tumour weight at the time of treatment: 200 mg/kg caused 0 and 100% mortality in mice bearing tumour nodules under 50 and over 300 mg, respectively. When anti-TNF-alpha antibodies were given after FAA treatment, the toxicity was greatly reduced (3/14 mice died compared with 10/15).