Selective radiosensitization of the hypoxic cells of mouse tumors with the nitroimidazoles metronidazole and Ro 7-0582
A study was made of the effect of two nitroimidazoles, metronidazole and the Roche product Ro 7-0582, on the radiosensitivity of the EMT6 mouse tumor. Both drugs at the high concentration of 1.0 and 1.2 mg/g (metronidazole and Ro 7- 0582, respectively) reduced the slope of the resistant portion of the tumor cell survival curve. The radiosensitization was maximum at 30 min after intraperitoneal injection, and was gradually lost during the next 6 hr. Experiments performed to determine the degree of radiosensitization as a function of amount of Ro 7-0582 injected showed near-maximum radiosensitization of the hypoxic cells (as judged by the slope change of the resistant portion of the cell survival curve) at concentrations above 0.1 mg/g. At these concentrations dose modification factors for the hypoxic tumor cells (DMF) of approximately 2.5 were obtained. A tumor control study with the MDAH/MCa4 mammary carcinoma confirmed both the high DMF (= 2.3) at high Ro 7-0582 concentration, and the lack of a large reduction in the DMF (greater than 1.8) when the concentration was reduced to 0.3 mg/g. There was some cytotoxicity at the high drug doses. Concentrations of Ro 7-0582 of both 0.3 and 1.0 mg/g radiosensitized the normal skin at doses of 3000 rad and above, presumably due to lack of full oxygenation of this tissue. (auth)
- Research Organization:
- Stanford Univ., CA
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-33-015075
- OSTI ID:
- 4116038
- Journal Information:
- Radiat. Res., v. 64, no. 3, pp. 633-647, Journal Name: Radiat. Res., v. 64, no. 3, pp. 633-647; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
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