Wang C Y, Nagase H, Lee M S, Ksebati M B
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Chem Res Toxicol. 1992 Mar-Apr;5(2):183-7. doi: 10.1021/tx00026a006.
The present study investigated the reaction of carcinogenic electrophiles with beta-diketones which possess an active methylene group. N-Acetoxy-2-(acetylamino)fluorene bound to tRNA at 37 degrees C, pH 7.0, and this reaction was inhibited by 4,4,4-trifluoro-1-phenyl-1,3-butanedione or 2-thenoyltrifluoroacetone. N-Acetoxy-2-(acetylamino)fluorene reacted with these active methylene compounds to form transitory 3-substituted 2-(acetylamino)fluorene intermediates, which, following cleavage of the trifluoroacetyl group, yielded 3-phenacyl-2-(acetylamino)fluorene or 3-(2-thenoylmethyl)-2-(acetylamino)fluorene. N-Acetoxy-2-[(trifluoroacetyl)amino]fluorene reacted with 4,4,4-trifluoro-1-phenyl-1,3-butanedione to yield two products, N-phenacyl-1-(trifluoroacetyl)-2-aminofluorene and N-phenacyl-3-(trifluoroacetyl)-2-aminofluorene. The ratio of these two products was approximately 1:2. The same N-phenacyl products were produced by incubation of the beta-diketone, N-hydroxy-2-(acetylamino)fluorene, and rat liver cytosol which catalyzed the formation of N-acetoxy-2-aminofluorene. Thus, the inhibitions by beta-diketones of nucleic acid-binding and bacterial mutagenesis of carcinogens are likely due to their trapping of the carcinogens.
本研究调查了致癌亲电试剂与具有活性亚甲基的β-二酮的反应。N-乙酰氧基-2-（乙酰氨基）芴在37℃、pH 7.0条件下与tRNA结合，该反应受到4,4,4-三氟-1-苯基-1,3-丁二酮或2-噻吩甲酰三氟丙酮的抑制。N-乙酰氧基-2-（乙酰氨基）芴与这些活性亚甲基化合物反应形成瞬时的3-取代-2-（乙酰氨基）芴中间体，在三氟乙酰基裂解后，生成3-苯甲酰甲基-2-（乙酰氨基）芴或3-（2-噻吩甲酰甲基）-2-（乙酰氨基）芴。N-乙酰氧基-2-[(三氟乙酰基)氨基]芴与4,4,4-三氟-1-苯基-1,3-丁二酮反应生成两种产物，N-苯甲酰甲基-1-（三氟乙酰基）-2-氨基芴和N-苯甲酰甲基-3-（三氟乙酰基）-2-氨基芴。这两种产物的比例约为1:2。通过β-二酮、N-羟基-2-（乙酰氨基）芴和催化N-乙酰氧基-2-氨基芴形成的大鼠肝细胞溶胶温育也产生了相同的N-苯甲酰甲基产物。因此，β-二酮对致癌物核酸结合和细菌诱变的抑制作用可能是由于它们捕获了致癌物。
