Chemotherapy of a Rat Brain Tumor Model by Innoculation of Ascites Hepatoma Cells

—Effects of ACNU and Adriamycin, and Their Tissue Concentrations—

Abstract

A rat brain tumor model was developed for chemotherapy by percutaneous innoculation of ascites hepatoma cells (AH-7974) through an optic canal.
Using this in vivo model, efficacy of ACNU, one of the nitrosourea compounds, and adriamycin, an anthracycline derivative, was studied. The median survival time was significantly prolonged by a single injection of 10 mg/kg of ACNU on the 4th post-innoculation day and by double injections on the 4th and the 7th days when compared with the control group. No significant prolongation of life span was obtained by adriamycin except in the group given 5 mg/kg on the 7th day.
The response of ascites hepatoma cells to these drugs was also studied using in vitro and subcutaneous tumor systems. The in vitro growth of the tumor cells was significantly suppressed by ACNU and adriamycin.
The tissue concentrations of these drugs in both subcutaneous tumor and brain were equal. However, it was found that the tumor-brain ratio was different for these drugs because the normal brain was more permeable to ACNU than to adriamycin. This might be one reason why ACNU is a potent drug for brain tumors as well as for systemic tumors.