Combined effects of misonidazole, microwave hyperthermia, and X-rays on the in vivo sister chromatid exchanges and chromosomal abnormalities of the dbrB tumor and on the survival of its host.

A rapidly proliferating mammary adenocarcinoma designated dbrB growing s.c. in isogeneic female DBA/1J mice in their 278th passage of transfer constituted the experimental host tumor system. A 5-bromodeoxyuridine pellet (2.5 mg/g body weight) was used for sister chromatid exchange analysis of the 0.5-cu cm dbrB tumor. Experiments were performed on Group I, untreated tumor-bearing mice, and Group II, tumor-bearing mice treated with triple agents: misonidazole (1 mg/g body weight); 42.5 degrees microwave hyperthermia for 10 min; and X-rays administered singly or in combination at about 4 hr following the implantation of a 5-bromodeoxyuridine pellet. The X-ray treatments consisted of 400, 1000, 1500, and 2000 rads, respectively. X-rays and hyperthermia were delivered to the tumors directly, while the rest of the mouse body was lead shielded. Survival of the untreated tumor-bearing control mice in Group I was 12 +/- 3 (S.D.) days, whereas the mice in Group II whose tumors were treated with misonidazole, hyperthermia, and 2000 rads of X-rays survived 27 +/- 3 days. 5-bromodeoxyuridine per se had no effect on the survival of the experimental mice. Only a dose of 400 rads administered to the dbrB tumors permitted detailed evaluation of chromosomal analyses, whereas the larger doses of radiation caused cellular destruction. Simultaneous treatment with triple agents resulted in sister chromatid exchanges of 33.78 +/- 0.39/cell as compared with sister chromatid exchanges of 14.74 +/- 0.39/cell of untreated control tumors. This mode of treatment also induced various types of chromosomal abnormalities in the tumor cells.