Vascular permeability and cell kinetics of ethylnitrosourea (ENU)-induced rat brain tumours

Vascular permeability and proliferative activity of ethylnitrosourea (ENU)-induced rat brain tumours were studied by intravenous injection of Evans blue dye (EB) and by bromodeoxyuridine (BrdU) uptake examinations. Tumours induced by ENU showed various histologial types, and they were oligodendrogliomas, mixed oligo-astrocytomas, mixed oligo-ependymomas, astrocytomas, anaplastic astrocytomas, polymorphic gliomas, and ependymomas. The labelling indexes (LIs: the ratio of BrdU-labelled cells to total cells) of tumour and vascular component cells in the tumour were high in anaplastic astrocytomas, polymorphic gliomas and ependymomas, but low in oligodendrogliomas. EB stained anaplastic astrocytomas, polymorphic gliomas and ependymomas deeply, but did not penetrate oligodendrogliomas. In mixed gliomas, EB staining and the LIs of tumour cells were not uniform. After intracarotid infusion of hyperosmolar mannitol into tumour-bearing rats, tumour staining with EB and the LIs of tumour cells were not increased, whereas the penetration of EB into the normal brain was drastically increased. Therefore it is not likely that the delivery of chemotherapeutic drugs to the tumour could be increased by intracarotid infusion of hyperosmolar manitol. Our data suggest that the vascular permeability of tumour vessels is highly correlated with the high proliferative activity of tumour and its vascular cells.