O6-alkylguanine-DNA alkyltransferase activity in normal human tissues and cells

Normal adult human tissues and cultured bronchial epithelial cells and fibroblasts exhibit 06-alkylguanine-DNA alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkylation lesion 06-methylguanine from DNA. The amount repaired by extracts of liver, peripheral lung, and colon extracts was proportional to the amount of extract protein. Repair of O6-methylguanine led to stoichiometric regeneration of guanine in the DNA and stoichiometric formation of S-methylcysteine in protein. Alkyltransferase activity varies in the different human tissues tested in the decreasing order of liver > colon > esophagus > peripheral lung > brain. Extracts of lung tissues, cultured human bronchial epithelial cells, and fibroblasts had similar alkyltransferase activities. Various human tissues exhibit 2- to 10fold higher alkyltransferase activity than corresponding rat tissues. Whereas the interindividual variation of the activity was 4-to 5-fold in ten or more human lung and colon specimens, the interindividual variation in the inbred rat was less than 20%. The present results show that different human tissues and cells have a several-fold higher capacity to repair 06-methyiguanine in DNA than do rat tissues and that the repair process occurs via a mechanism similar to that shown previously in other mammalian cells and Escherichia coli.