Further investigations of the effects of the hypoxic-cell radiosensitizer, Ro-07-0582, on local control of a mouse tumour

Abstract

Summary.-The tumour used, designated MT1, is a more radiosensitive form of the anaplastic MT tumour previously described. No explanation for the increased radiosensitivity was found, but it was shown not to be due to infection or to a change in immunological status, growth rate or histology. The sensitivity has remained constant throughout the present work.No cytotoxicity in the tumour was observed when 1 mg/g body weight of Ro-07-0582 was injected immediately after a single dose of X-rays; indeed a small protective effect was seen.A radiosensitization enhancement of 1P5 was achieved with a relatively low drug dose of Ro-07-0582 in a 5F/4d fractionated regime.The interval between the injection of a low dose of Ro-07-0582 and the start of irradiation was found to be critical, the optimum interval being 45-60 min.The subsequent incidence of distant metastases was not increased by the use of Ro-07-0582 at the time of "primary" tumour irradiation.

Radiation sensitization and chemopotentiation: Rsu 1069, a compound more efficient than misonidazole in vitro and in vivo

“…Figure 2 shows the concentration dependence of the enhancement ratios for RSU 1069. The ratios for hypoxic cells irradiated in the presence of MISO (dashed line in Figure 2) were similar to those reported previously for this cell line (Adams et al, 1976 Radiosensitization It is known that, due to pharmacokinetic considerations, the time at which a sensitizer is administered to tumour-bearing mice prior to irradiation can greatly influence the observed radiation response (Sheldon & Hill, 1977b;McNally et al, 1978;Brown & Yu, 1980). Therefore in initial experiments RSU 1069 was given i.p.…”

“…with RSU 1069 in saline, and locally irradiated with 230 kV X-rays (Sheldon & Hill, 1977a). Tumour response was determined either by an in vitro soft agar clonogenic assay (Sheldon et al, 1982) or by the probability of local tumour control at 80 days (Sheldon & Hill, 1977b). The soft agar clonogenic assay was also used in the chemopotentiation studies, where male mice bearing the MT tumour were treated i.p.…”