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Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20205 [C. C. H.]; Department of Physiology and Specialized Cancer Research Center, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033 [A. E. P.]; Department of Forensic Medicine, Karolinska Institutet, S-104 01 Stockholm 60, Sweden [R. C. G.]; and Department of Pathology, University of Maryland, School of Medicine, Baltimore, Maryland 21201 [B. F. T.]
Normal adult human tissues and cultured bronchial epithelial cells and fibroblasts exhibit O6-alkylguanine-DNA alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkylation lesion O6-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 10-fold 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 O6-methylguanine 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.
1 Supported by Swedish Cancer Society Grant 1623-B84-02TB for part of this study.
2 Supported by Grant CA 18137.
3 To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, Building 37, Room 2C09, National Cancer Institute, Bethesda, MD 20205.
Received 12/19/83. Accepted 4/ 3/84.
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