Selective Radiosensitization of the Hypoxic Cells of Mouse Tumors with the Nitroimidazoles Metronidazole and Ro 7-0582

Enhanced cytotoxicity of antineoplastic agents following prolonged exposure to misonidazole

“…In addition to preferentially sensitizing hypoxic cells, MISO is also preferentially cytotoxic to cells deficient in 2. This has been reported for single cells in vitro (Hall & Roizin-Towle, 1975;Mohindra & Rauth, 1976;Moore et al, 1976;Stratford & Adams, 1977), for cells in multicellular spheroids (Sutherland et al, 1976) and in solid tumours in experimental animals (Denekamp & Harris, 1976;Brown, 1975;Fowler et al, 1976). This cytotoxicity also proved to be strongly dependent on temperature (Stratford & Adams, 1977;.…”

Misonidazole enhancement of acute and late radiation injury to the rat spinal cord

“…It is already clear that these drugs can radiosensitize and possibly be toxic to solid tumours in the laboratory and the clinic, but what is not clear is whether these effects are expressed selectivelv in the tumour tissues. Under appropriate experimental conditions, it has been possible to demonstrate radiosensitization of the murine skin (Brown, 1975;Yuhas et al, 1977) and testis (Suzuki et al, 1977) after injection of misonidazole (Ro-07-0582, MIS). One couild argue logically that these observations would not limit the clinical application of MIS because the tissues involved are seldom radiation-dose limiting, and the demonstration of radiosensitization required single large doses of radiation which are far beyond those used clinically.…”

A novel hypoxia-dependent 2-nitroimidazole KIN-841 inhibits tumour-specific angiogenesis by blocking production of angiogenic factors

“…The use of a radiosensitiser with an affinity for hypoxic tumour cells and a probe for the detection and quantitation of hypoxia regions in tumours is important for developing appropriate therapeutic modalities against hypoxic tumour cells. Nitroimidazole derivatives have been studied extensively for use as radiosensitisers (Sheldon et al, 1974;Brown, 1975) and molecular markers of hypoxic regions in solid tumours (Walton and Workman, 1987;Aboagye et al, 1995). 2-Nitroimidazole derivatives, such as misonidazole and etanidazole, have been reported to have potent radiosensitising ability (Sheldon et al, 1974;Brown et al, 1981), and have been clinically studied regarding their application in the radiotherapy of patients with malignant tumours (Chang et al, 1998;Grigsby et al, 1999).…”