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Enhancement of Radioresponse of a Mouse Mammary Carcinoma to Combined Treatments with Hyperthermia and Radiosensitizer Misonidazole¹

Cancer and Radiobiological Research Laboratory, Department of Biology, New York University, New York, New York 10003 [A. G., D. B.], and Division of Biostatistics, School of Public Health, Columbia University, New York, New York 10032 [A. B.]

The regrowth delay of a transplanted syngeneic mouse mammary carcinoma designated MT₂ was used to estimate the effects of three-fold combination treatments: X-irradiation; hyperthermia and radiosensitizer; and misonidazole (Ro-07-0582). The experiment entailed five groups of experimental mice: untreated control; X-rays alone; X-rays plus hyperthermia (42–43°); X-rays plus misonidazole; and X-rays plus hyperthermia plus misonidazole. X-Ray treatments consisted of 4000 rads administered locally to the tumors in two equal fractions at a 48-hr interval. Misonidazole (0.67 mg per g body weight) was injected i.p. 30 min before exposure to X-irradiation. Hyperthermia was administered 10 min prior to and for 17 min during irradiation.

The regrowth delay factor of 3.9 was obtained by administering combined treatments of the three agents (X-rays plus hyperthermia plus misonidazole). The enhancing effect on a syngeneic mouse mammary adenocarcinoma by the modality of treatment herein described lends support to the usefulness of combining X-rays with other agents in the treatment of neoplasms.

¹ This investigation was supported in part by Grant PDT-107 from the American Cancer Society and in part by Grant CA-12076, awarded by the National Cancer Institute, Department of Health, Education, and Welfare. Some of these results were presented in discussion by A. Goldfeder at the Meeting of the European Study Group for Cell Proliferation held in Paris, France, March 1978, and at a meeting on hyperthermia at Villejuif, France, also in March 1978.

² To whom requests for reprints should be addressed, at Department of Biology, New York University, 100 Washington Square, New York, N. Y. 10003.

Received 9/ 6/78. Accepted 4/24/79.