Yoshikawa T, Kimura S, Hatano T, Okamoto K, Hayatsu H, Arimoto-Kobayashi S
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
Food Chem Toxicol. 2002 Aug;40(8):1165-70. doi: 10.1016/s0278-6915(02)00060-1.
Previously we reported that beer is antimutagenic against several food-derived mutagens including heterocyclic amines. We describe here the isolation and identification of pseudouridine from beer as an antimutagenic substance against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). All of the 17 samples of beer tested showed inhibition of the MNNG mutagenicity in Salmonella. Extensive fractionation through chromatography of the active components from a freeze-dried beer sample gave six antimutagenic fractions. One contained pseudouridine, as characterized by the UV spectra, nuclear magnetic resonance, and co-chromatography in HPLC. Pure pseudouridine inhibited the mutagenicity of MNNG in a dose-dependent manner. The amount of pseudouridine in the beer sample, estimated at about 0.4 mg/100 ml beer, can account for 3% of the total antimutagenicity of beer. Thus, the major active components in beer remain to be identified. The role of pseudouridine in inhibiting the mutagenicity of MNNG is to be studied further. Among analogs of pseudouridine, spongouridine, but not uridine, was antimutagenic against MNNG. The bacterial mutagenicity of another methylating agent N-methyl-N-nitrosourea was also inhibited by pseudouridine. Pseudouridine is the first example among nucleosides to be shown to possess an antimutagenic property.
此前我们报道过，啤酒对包括杂环胺在内的几种食物来源的诱变剂具有抗诱变作用。我们在此描述从啤酒中分离和鉴定假尿苷，它是一种针对N-甲基-N'-硝基-N-亚硝基胍（MNNG）的抗诱变物质。所测试的17个啤酒样品均显示出对沙门氏菌中MNNG诱变性的抑制作用。通过对冻干啤酒样品中的活性成分进行色谱广泛分级分离，得到了六个抗诱变级分。其中一个含有假尿苷，通过紫外光谱、核磁共振以及高效液相色谱中的共色谱法得以鉴定。纯假尿苷以剂量依赖方式抑制MNNG的诱变性。啤酒样品中假尿苷的含量估计约为0.4毫克/100毫升啤酒，可占啤酒总抗诱变性的3%。因此，啤酒中的主要活性成分仍有待鉴定。假尿苷在抑制MNNG诱变性中的作用有待进一步研究。在假尿苷的类似物中，海绵尿苷对MNNG具有抗诱变作用，而尿苷则没有。另一种甲基化剂N-甲基-N-亚硝基脲的细菌诱变性也受到假尿苷的抑制。假尿苷是核苷中首个被证明具有抗诱变特性的例子。
