Chloroethylnitrosourea (
CENU)
chemotherapy has yielded limited benefit on survival of malignant
brain tumors. Intracarotid administration of
CENU is expected to have the advantage of increasing
drug concentration reaching
tumors. To understand basic knowledge of intracarotid
chemotherapy, we monitor changes of proliferating rate after intracarotid injection of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (
ACNU), using a
bromodeoxyuridine (
BUdR) labeling index (LI) in transplanted
brain tumors of three cell strains. C6-2
tumor cells were in vitro sensitive to
ACNU, and C6-2/
ACNU and C6-1 cells were resistant. The
drug sensitivity to
ACNU was as follows: 11.9 microM in the C6-2 cells, 46.0 microM in the C6-2/
ACNU cells, and 49.7 microM in the C6-1 cells at SD10, which gives 10% survival of clonogenic cells. The intracarotid
ACNU at a dose of 30 mg/kg abruptly decreased the LI to 11% (mean) from 36% in C6-2 transplanted
tumors. The LI remained low between 12 and 48 hours after, and then increased to the pretreatment level by 96 hours. In contrast, the LI of C6-1
tumors transiently fell to 15% from 42% at 12 hours after the injection, and subsequently increased to 36% at 24 hours and 37% at 48 hours. These results indicate that intracarotid
ACNU administration shortly suppresses proliferating activity of
tumors and that combined and alternating
chemotherapy are mandatory for enhancing effectiveness of
brain tumor chemotherapy.