DNA excision-repair deficiency of human peripheral blood lymphocytes treated with chemical carcinogens.
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.
D000099:Acetoxyacetylaminofluorene / Q000378:metabolism / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D002273:Carcinogens; D003208:Concanavalin A; D000099:Acetoxyacetylaminofluorene; D004247:DNA; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea