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Low O⁶-Alkylguanine DNA Alkyltransferase Activity in the Peripheral Blood Lymphocytes of Patients with Therapy-related Acute Nonlymphocytic Leukemia¹

University of Chicago Cancer Research Center and Departments of Molecular Genetics and Cell Biology [D. S., B. S.], Medicine [T. K., R. L.], Radiation and Cellular Oncology [J. L. S.], and Statistics [P. M.], The University of Chicago, Chicago, Illinois 60637

Chemotherapeutic agents such as procarbazine, which produce methylated bases in DNA, are used to treat many Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients. A small proportion of such patients develop secondary malignancy. We examined the possibility that those patients who develop secondary malignancy have low endogenous levels of O⁶-alkylguanine DNA alkyltransferase (AGT) activity and are therefore more sensitive to the mutagenic and carcinogenic effects of their treatment. We assayed AGT activity in peripheral blood lymphocytes from patients with HD, NHL, acute nonlymphocytic leukemia (ANLL) de novo, and therapy-related ANLL, as well as a group of normal control subjects. Studies in normal controls showed that at least over a short term of 1 week, individuals have characteristic AGT levels, although some individuals sampled repeatedly over several months showed high variation. Mean AGT activities ± SE for the various groups studied were (fmol/µg of DNA): normal control group, 7.05 ± 0.36; HD and NHL patients (prior to treatment), 4.97 ± 0.42; HD-NHL patients receiving procarbazine, 3.88 ± 0.44; ANLL de novo, 7.78 ± 1.72; and therapy-related ANLL, 4.30 ± 0.58. AGT activity decreased in the peripheral blood lymphocytes of some individuals taking procarbazine. The mean AGT activity in the procarbazine-treated patients was low, as was the activity for the therapy-related ANLL patients.

¹ This work was supported by a Program Project Grant from the National Cancer Institute (CA40046).

² To whom requests for reprints should be addressed, at Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58th Street, Chicago, IL 60637.

Received 12/ 1/87. Revised 2/23/88. Accepted 3/ 3/88.

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