THE IN-VIVO INTERACTION BETWEEN FLAVONE ACETIC-ACID AND HYPERTHERMIA

The in vivo interaction between flavone acetic acid (FAA) and hyperthe rmia was studied in a C3H mammary carcinoma grown in the feet of femal e CDF1 mice and in normal foot skin. FAA was intraperitoneally injecte d prior to local tissue heating in restrained non-anaesthetized animal s. Alone, FAA at doses of 100 mg/kg and above, inhibited tumour growth in a dose-dependent fashion. FAA also enhanced the tumour response to heat, the effect being dependent on both the time interval between th e two modalities and the FAA dose, the greatest effect occurring when FAA doses of greater than or equal to 150 mg/kg preceeded heat by 3-48 h. These effects of FAA correlated with the drug's ability to decreas e tumour blood perfusion measured using the RbCl extraction procedure. Injecting 150 mg/kg FAA 3 h before heating (42.7 degrees C) resulted in a 2.2-fold increase in tumour heat damage, but had little effect on the response of normal foot skin in non-tumour-bearing mice. However, this treatment gave a 2.0-fold increase in normal tissue damage when the skin experiments were repeated in tumour-bearing animals. These ef fects in skin occurred in the absence of any blood perfusion changes, but appeared to be associated with FAA-induced TNF-alpha production.