Abstract
Two types of mouse tumour have been used to study the radiomodifying actions of Misonidazole (MISO) and WR-2721 when used alone and in combination with each other. Single dose studies were performed in both of the tumours and fractionated studies were performed on the anaplastic carcinoma, CA MT. Radioprotection with WR-2721 was seen in both tumours, being most marked at low X-ray doses. The protection was more obvious and the sensitization by MISO less in the fractionated experiment. The combination of MISO and WR-2721 gave an intermediate response compared with either drug used alone, resulting in some sensitization with single doses and an overall protection with repeated small doses. An interactive toxicity of the 2 drugs was also observed, suggesting an additive effect when assessed in terms of lethality. These studies indicate that the effects of both MISO and WR-2721 are dependent upon the oxygen status of the cells in the tumour, and that MISO can act in an oxygen-mimetic manner to modify the radioprotection observed with WR-2721.
Highlights
Materials and methodsSpecific-pathogen free albino mice of the strain WHT/Gy f BSVS were used in all experiments
We have studied the modification of the radiation response of 2 mouse tumours by the radiosensitizer Misonidazole (MISO) and the radioprotector WR2721, used alone or in combination
This paper reports a similar effect in tumours: Reduction of tumour radiosensitization by MISO is seen if WR-2721 is present, both for single doses and a 5-fraction schedule
Summary
Specific-pathogen free albino mice of the strain WHT/Gy f BSVS were used in all experiments. 1) Fibrosarcoma SA FA a spontaneous tumour which arose in this laboratory in 1974 and since has been serially transplanted in isogeneic inbred mice It is a moderately differentiated fibrosarcoma with a doubling-time of about 4 days at 7mm mean diameter. Locally-controlled tumours were included in the analysis and given an arbitrary regrowth delay (Denekamp et al, 1980) corresponding to the longest time at which recurrence had ever been observed for that tumour type (e.g. 75 days for CA MT) Such groups have an upward arrow on their error bars, indicating that the mean regrowth delay is a minimum estimate. It was dissolved in sterile saline and 1 ml per 30 g mouse was given 45 min before irradiation, i.e. 15 min before the radioprotector
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