a comparison of electron affinic drugs as radiosensitizers and cytotoxic agents

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Their survival is being examined with the Kaplan-Meier Probability Plot and non-parametric tests. At this time, too few patients have been entered for meaningful survival curves to be presented. The non-parametric test (Wilcoxon-Gehan Test) indicates no differences among the three groups. (87) A COMPARISON OF ELECTRON AFFINIC DRUGS AS RADIOSENSITIZERS AND CYTOTOXIC AGENTS Eric J. Hall and Myles Astor Radiological Research Laboratory, College of Physicians and Surgeons of Columbia University, New York, N.Y. A number of electron affinic compounds have been tested as radiosensi- tizers of hypoxic cells and also for their ability to kill hypoxic cells directly. The present study focuses attention of two Z-nitroimidazoles, Ro-07-0582, known as misonidazole and Ro-07-0741. In experiments with Chinese hamster (V79) cells exposed to 60 Cobalt gamma rays or high energy cyclotron produced neutrons, Ro-07-0741 proved to be a slightly more effective radiosensitizer than misonidazole; however, it is also significantly more cytotoxic. For both compounds, the drug concentration required to kill 90% of a hypoxic cell population was found to be inversely proportional to the square of the exposure time to the drug at 37.5 C. Preliminary experiments have also been performed with the quinone MTDQ, which at comparable concentrations proves to be a significantly more potent radiosensitizer than misonidazole. However, it is much less water soluble than the nitroimidazoles, and this may limit its usefulness in vivo. (This investigation was supported by contract EP-78-S-02-4733 from the Department of Energy and grant no. CA-18506 awarded by the National Cancer Institute, DHEW.) 038) A STUDY OF THE EFFECTS OF RADIATION THERAPY COMBINED WITH POSSIBLE POTENTIATING AGENTS ON ARTIFICIALLY INDUCED VX2 LUNG METASTASES IN RABBITS David S. Gooden, Ph.D., Delia Beju, Ph.D. Natalie Warren Bryant Cancer Center and W.K. Warren Medical Research Center Tulsa, Oklahoma Using artificially induced lung metastases of VX2 carcinoma in New Zea- land rabbits, we assessed the effects of Lucanthone, Metronidazol (Flagyl) and C. parvum used individually in combination with X-ray radiation upon the evolution of the disease. The selected adjuvants represent three different mechanisms by which potentiation might be realized. Lucanthone promotes ion- izing radiation induced denaturation of DNA and inhibits postirradiation re- covery of cell RNA synthesis. Metronidazol mimics the oxygen effect in tu- mor tissue. C. parvum is a nonspecific immunostimulant which may possess 134

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Page 1: A comparison of electron affinic drugs as radiosensitizers and cytotoxic agents

Their survival is being examined with the Kaplan-Meier Probability Plot and non-parametric tests. At this time, too few patients have been entered for meaningful survival curves to be presented. The non-parametric test (Wilcoxon-Gehan Test) indicates no differences among the three groups.

(87) A COMPARISON OF ELECTRON AFFINIC DRUGS AS RADIOSENSITIZERS AND CYTOTOXIC AGENTS

Eric J. Hall and Myles Astor

Radiological Research Laboratory, College of Physicians and Surgeons of Columbia University, New York, N.Y.

A number of electron affinic compounds have been tested as radiosensi- tizers of hypoxic cells and also for their ability to kill hypoxic cells directly. The present study focuses attention of two Z-nitroimidazoles, Ro-07-0582, known as misonidazole and Ro-07-0741. In experiments with Chinese hamster (V79) cells exposed to 60 Cobalt gamma rays or high energy cyclotron produced neutrons, Ro-07-0741 proved to be a slightly more effective radiosensitizer than misonidazole; however, it is also significantly more cytotoxic. For both compounds, the drug concentration required to kill 90% of a hypoxic cell population was found to be inversely proportional to the square of the exposure time to the drug at 37.5 C.

Preliminary experiments have also been performed with the quinone MTDQ, which at comparable concentrations proves to be a significantly more potent radiosensitizer than misonidazole. However, it is much less water soluble than the nitroimidazoles, and this may limit its usefulness in vivo.

(This investigation was supported by contract EP-78-S-02-4733 from the Department of Energy and grant no. CA-18506 awarded by the National Cancer Institute, DHEW.)

038) A STUDY OF THE EFFECTS OF RADIATION THERAPY COMBINED WITH POSSIBLE

POTENTIATING AGENTS ON ARTIFICIALLY INDUCED VX2 LUNG METASTASES IN RABBITS

David S. Gooden, Ph.D., Delia Beju, Ph.D.

Natalie Warren Bryant Cancer Center and W.K. Warren Medical Research Center Tulsa, Oklahoma

Using artificially induced lung metastases of VX2 carcinoma in New Zea- land rabbits, we assessed the effects of Lucanthone, Metronidazol (Flagyl) and C. parvum used individually in combination with X-ray radiation upon the evolution of the disease. The selected adjuvants represent three different mechanisms by which potentiation might be realized. Lucanthone promotes ion- izing radiation induced denaturation of DNA and inhibits postirradiation re- covery of cell RNA synthesis. Metronidazol mimics the oxygen effect in tu- mor tissue. C. parvum is a nonspecific immunostimulant which may possess

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