O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY OF HUMAN-MALIGNANT GLIOMA AND ITS CLINICAL IMPLICATIONS

Activity of the DNA repair protein O-6-alkylguanine-DNA alkyltransfera se (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic ag ents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT act ivity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. T here were wide variations in AGT activity between individuals. No sign ificant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recur rent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma , tumors possessing higher AGT activity tended to be less responsive t o post-operation remission-induction therapy including CENUs. The resu lt of the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT) chemosensitivity assay by using the corresponding surgical specim ens suggested a close relationship between cellular resistance to CENU s and AGT activity. It was found to be unlikely that a short term admi nistration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of t he relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.