Irradiation and BCNU effects in the stroma in a rat transplanted glioma model: analysis of cerebral tumor bed effect.

F-344 rats were treated with whole-brain fractionated or unfractionated 137Cs at several time intervals up to 6 weeks before they received intracerebral grafts of an ethylnitrosourea-induced rat astrocytoma (36B-10). Rats treated with a single dose of 18 Gy at 3- and 2 week intervals prior to tumor implantation died earlier than unirradiated control tumor recipients (P less than 0.05, log rank sum test). Delivered 2 weeks prior to tumor grafting single doses of 10, 15, and 20, but not 5 Gy also reduced animal life span (P less than 0.05). Similarly, a total dose of 38 but not 28.5, 19, or 9.5 Gy, each delivered in five daily fractions 2 1/2 weeks before tumor grafting, shortened survival (P less than 0.05). Chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg) alone or in combination with a single-dose of irradiation of 18 Gy 3 weeks preceding transplantation showed no effect on animal survival. Unirradiated control tumors demonstrated sheets of densely-packed isomorphic astrocytes, perivascular brain parenchymal invasion, sparse, thin-walled vasculature, frequent mitoses, but little necrosis or hemorrhage. The tumors of rats irradiated before transplantation showed large areas of confluent necrosis associated with microvascular thrombosis, edema, and multifocal acute hemorrhages. These survival results and morphological changes indicate that the cerebral tumor bed effect involves early animal death and extensive morphological changes in the tumors; and they suggest that tumor cell death in irradiated brain tumors may, in part, result from radiation-induced vascular injury.