O6-alkylguanine-DNA alkyltransferase activity in human brain and brain tumors.

It was found that extracts from human brain catalyzed the transfer of methyl groups from O6-methylguanine in methylated double-stranded DNA to a cysteine residue in a protein of mol. wt. approximately 22 000. This O6-alkylguanine-DNA alkyltransferase had properties similar to those previously characterized from rodent liver, human liver, cultured human cells and E. coli. The alkyltransferase activity of human brain was considerably greater than that reported for rat brain, but was significantly less than the activities found in human liver and other tissues. The activity was found in both normal brain samples (peritumoral material which contained no tumor infiltration) and in a variety of brain tumors. The highest activity was found in meningeomas and neurinomas, but most tumors with the exception of some gliomas had higher activities than the normal brain. All 23 tumor samples examined in this study had alkyltransferase activity in contrast to published reports showing that approximately 35% of human brain-tumor-derived lines grown in culture lacked this activity. This discrepancy may be due to the cellular polymorphism of the tumors, but also suggests that complete lack of the alkyltransferase is not a common occurrence in human brain tumors.