title: Induction of hypoxia in the KHT sarcoma by tumour necrosis factor and flavone acetic acid.
abstract: The interaction of FAA or TNF with radiation was studied in the murine KHT sarcoma. When used alone both agents showed a dose- and time-dependent toxicity towards the tumour cells and significantly reduced tumour blood flow within 1 h of treatment. When used in combination with radiation, both TNF and FAA caused an increase in the fraction of hypoxic cells in the KHT tumour. This was assessed by an in vivo/in vitro clonogenic assay and by a comparison with the radioprotection provided by clamping tumours prior to and during irradiation. When TNF was given at a dose of 2.5 X 10(5) U/kg an increase in tumour hypoxia was seen after 30 min. Close to 100% radiobiological hypoxia was reached by 1 h after treatment, lasting for up to 16 h. Doses of TNF below 0.25 X 10(5) U/kg did not induce levels of hypoxia comparable to clamping when administered 3 h prior to irradiation. Similarly, FAA produced a rapid increase in tumour hypoxia: a dose of 200 mg/kg induced close to 100% radiobiological hypoxia when give 1 h prior to irradiation. Complete tumour hypoxia was still apparent 18 h after treatment with FAA. Administered doses of FAA below 100 mg/kg did not produce close to 100% radiobiological hypoxia when administered 3 h prior to irradiation.
authors.affiliation: Medical Research Council Radiobiology Unit, Chilton, Didcot, Oxford, UK.
authors.forename: H S
authors.initials: HS
authors.lastname: Edwards
authors.forename: J C
authors.initials: JC
authors.lastname: Bremner
authors.forename: I J
authors.initials: IJ
authors.lastname: Stratford
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects*; D003131:Combined Modality Therapy; D005419:Flavonoids / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; C049328:flavone acetic acid