O6-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

Abstract

The activity of O⁶-methylgaunine-DNA methyltransferase (O⁶-MT), which removes O⁶-methyl residues from O⁶-methyIguanine-DNA leading to cell death, has been reported to correlate with sensitivity to nitrosoureas used for chemotherapy of gliomas. We determined O⁶-MT activity in tumors and matched brain tissue from patients with gliomas. Histological diagnoses were: six malignant astrocytomas, two glioblastomas, two oligodendrogliomas, one ependymoma, and one medulloblastoma. In all cases but one, the activity ranged widely from 39 to 258 fmol/mg protein extract. The wide range of activity of the tumor tissue may indicate varying degree of sensitivity to nitrosoureas. The activity of brain tissue, available from the peritumoral region of five cases, varied between 38 to 415 fmol/mg. Four of the five regions showed a higher value than the respective tumor, and one showed a lower value.