Low 06-Alkylguanine DNA AIkyItransf erase Activity in the Peripheral Blood Lymphocytes of Patients with Therapy-related Acute Nonlymphocytic Leukemia1

Chemotherapeutic agents such as procarbazine, which produce meth ylated 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 endoge nous levels of 06-alkylguanine DNA alkyltransferase (ACT) activity and are therefore more sensitive to the mutagenic and carcinogenic effects of their treatment. We assayed ACT activity in peripheral blood lympho cytes from patients with HD, NHL, acute nonlymphocytic leukemia (ANLL) ile 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 ACT levels, although some individuals sampled repeatedly over several months showed high variation. Mean AGT activities ±SE for the various groups studied were (fmol/Mgof DNA): normal control group, 7.05 ±OJ6; 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 ±O.S8. AGT activity decreased in the peripheral blood lymphocytes of some individuals taking procarbazine. The mean AGT activity in the procarbazine-treatedpatients was low, as was the activity for the therapy-related ANLL patients.