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O⁶-Methylguanine-DNA Methyltransferase in Human Normal and Tumor Tissue from Brain, Lung, and Ovary¹

Long Island Jewish Medical Center and Albert Einstein College of Medicine, New Hyde Park, New York 11042 [M. C., R. D., S. C., S. S., M. G., L. K., L. B. K., A. W., M. S.], and Applied Genetics, Inc., Freeport, New York 11520 [D. Y.]

The resistance of human tumor strains in culture to cell killing by alkylating nitrosoureas is correlated with their levels of the DNA repair activity O⁶-methylguanine-DNA methyltransferase. Strains with the Mer- phenotype have no activity and are extremely sensitive. However, the relationship between the sensitivity of human tumors in vivo and transferase levels is not known, and even the existence of Mer- human tumors in vivo has been questioned. In this study 73 human tumor and normal tissue samples from brain, lung, and ovary were assayed for transferase levels and methylpurine glycosylase activity. For each organ, transferase levels varied over 100-fold, and Mer- tumors were detected in each group. There was no correlation between transferase and glycosylase levels, indicating that the absence of transferase in some tumor samples was not an artifact due to necrosis or inactivation of enzymes in the extract.

¹ This research was supported in part by SBIR Contract N43-CN-07360 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.

Received 2/22/91. Accepted 6/ 6/91.

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