INDUCTION OF HYPOXIA IN THE KHT SARCOMA BY TUMOR-NECROSIS-FACTOR AND FLAVONE ACETIC-ACID

被引:21
|
作者
EDWARDS, HS
BREMNER, JCM
STRATFORD, IJ
机构
[1] Medical Research Council Radiobiology Unit, Chilton, Didcot, Oxford
基金
英国医学研究理事会;
关键词
D O I
10.1080/09553009114550381
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:419 / 432
页数:14
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