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DNA Excision-repair Deficiency of Human Peripheral Blood Lymphocytes Treated with Chemical Carcinogens¹

Department of Microbiology, The University of Chicago, Chicago, Illinois 60637

Human peripheral blood lymphocytes stimulated with concanavalin A for 72 hr have a 10-fold greater capacity to repair DNA damage induced by N-acetoxy-2-acetylaminofluorene than do unstimulated cells. The increased capacity of concanavalin A-activated cells to repair DNA is not observed after 24 hr in culture, a time at which stimulated cells have not begun to synthesize DNA. The maximum rate of repair synthesis obtained after treatment of stimulated cells with the "large patch"-inducing agent, N-acetoxy-2-acetylaminofluorene, is twice that obtained with methyl methanesulfonate, an agent inducing "small patch" repair. The difference between the maximum rates obtained with N-acetoxy-2-acetylaminofluorene and methyl methanesulfonate is 6-fold in a human lymphoblastoid line. Unstimulated lymphocytes show almost identical rates of repair after treatment with either N-acetoxy-2-acetylaminofluorene or methyl methanesulfonate. There is close correlation between the rate of N-acetoxy-2-acetylaminofluorene-induced repair synthesis and the loss of acetylaminofluorene adducts from DNA. Treatment of lymphocytes with methyl methanesulfonate leads to degradation of cellular DNA with the production of single-stranded regions. Such degradation is not observed with N-acetoxy-2-acetylaminofluroene. We conclude that the rate of excision repair is a function of the capacity of cells for DNA synthesis and that lymphocytes that do not synthesize DNA have a limited repair capacity and cannot be used to distinguish between large and small patch repair.

¹ Supported by grants from Energy Research and Development Administration [E(11-1)2040] and NIH (GM 07816, AI 12116, CA 14599-02).

² Present address: National Cancer Institute, NIH, Bethesda, Md.

³ Trainee in an immunology training program supported by NIH Grant AI 00452-03. Present address: Department of Surgery, Montefiore Hospital, Bronx, N. Y.

⁴ To whom requests for reprints should be addressed.

Received 8/25/75. Accepted 12/22/75.

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