Wang C Y, Lee M S, Zukowski K
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Mutat Res. 1991 Mar;262(3):189-93. doi: 10.1016/0165-7992(91)90021-u.
Effects of diacylmethanes on the mutagenicity of 2-naphthohydroxamic acid, methylnitrosourea, benzo[a]pyrene and aflatoxin B1 in S. typhimurium and the tRNA binding by benzo[a]pyrene and aflatoxin B1 were investigated. Acetylacetone, benzoylacetone and dibenzoylmethane inhibited the mutagenicity of 2-naphthohydroxamic acid, and dibenzoylmethane and 1,3-indandione inhibited that of methylnitrosourea, benzo[a]pyrene and aflatoxin B1. The binding to tRNA of benzo[a]pyrene and aflatoxin B1 was inhibited by benzoylacetone and dibenzoylmethane, and dibenzoylmethane, 1,3-indandione and 1,1,1-trifluoroacetylacetone, respectively. The inhibition of methylnitrosourea mutagenicity was observed when the bacteria were exposed concomitantly to the inhibitors and the mutagen, but not when they were exposed to the inhibitors 1 h after exposure to the mutagen. These results demonstrate that active methylene compounds can inhibit mutagenicity and nucleic acid-binding of chemical carcinogens presumably by trapping carcinogenic electrophiles, and they are potential anti-carcinogenic agents during the initiation stage.
研究了二酰基甲烷对鼠伤寒沙门氏菌中2-萘异羟肟酸、甲基亚硝基脲、苯并[a]芘和黄曲霉毒素B1致突变性的影响,以及苯并[a]芘和黄曲霉毒素B1与tRNA的结合情况。乙酰丙酮、苯甲酰丙酮和二苯甲酰甲烷抑制了2-萘异羟肟酸的致突变性,二苯甲酰甲烷和1,3-茚二酮抑制了甲基亚硝基脲、苯并[a]芘和黄曲霉毒素B1的致突变性。苯甲酰丙酮和二苯甲酰甲烷分别抑制了苯并[a]芘和黄曲霉毒素B1与tRNA的结合,二苯甲酰甲烷、1,3-茚二酮和1,1,1-三氟乙酰丙酮也分别抑制了它们与tRNA的结合。当细菌同时暴露于抑制剂和诱变剂时,观察到甲基亚硝基脲致突变性受到抑制,但当细菌在暴露于诱变剂1小时后再暴露于抑制剂时,则未观察到这种抑制作用。这些结果表明,活性亚甲基化合物可能通过捕获致癌亲电试剂来抑制化学致癌物的致突变性和与核酸的结合,并且它们在启动阶段是潜在的抗癌剂。