Skog K, Jägerstad M
Food Chemistry, Chemical Center, University of Lund, Sweden.
Mutat Res. 1990 Jun;230(2):263-72. doi: 10.1016/0027-5107(90)90064-b.
The formation of the mutagenic imidazoquinoxalines (MeIQx, DiMeIQx) was studied using a modification of a previous model system. Creatine or creatinine (0.9 mmole) was heated together with glycine (0.9 mmole) and various sugars (0.45 mmole) dissolved in diethylene glycol and water (3 ml, 5:1) for up to 15 min at 180 degrees C. This system produced the same amount of mutagenicity after 10 min at 180 degrees C as a previous one during 2 h of reflux boiling at 128 degrees C. MeIQx (4 nmole/mmole creatin(in)e) was the major mutagen produced together with minor amounts of DiMeIQx, both 4,8- and 7,8-DiMeIQx according to HPLC-MS. A few other mutagenic peaks were also separated on HPLC, but they were not identified. Varying the concentration (0-2.4 mmole) and type of monosaccharides and disaccharides greatly affected the yields of all the mutagenic compounds. Sugar in molar amounts lower than the creatin(in)e concentration increased the yield until an optimum was reached. In higher concentrations the formation of all the mutagens was markedly reduced. The same was found for glucose, fructose, sucrose, and lactose, though the monosaccharides showed the most pronounced inhibitory effects. The inhibition of the formation of the mutagenic compounds by an excess of sugars is proposed to be an effect of Maillard reaction products, which may block the formation of imidazoquinoxalines by attacking creatine. Support for this mechanism is given by data showing a lower recovery of unreacted creatine with increasing concentration of glucose and also by an inhibitory effect on the formation of these mutagens after adding a typical Maillard reaction product, 5-hydroxymethyl-2-furfural.
使用先前模型系统的一种改进方法研究了诱变剂咪唑并喹喔啉（MeIQx、DiMeIQx）的形成。将肌酸或肌酐（0.9毫摩尔）与溶解于二甘醇和水（3毫升，5:1）中的甘氨酸（0.9毫摩尔）及各种糖（0.45毫摩尔）一起在180℃加热长达15分钟。该系统在180℃加热10分钟后产生的诱变性与先前在128℃回流煮沸2小时的系统相同。根据高效液相色谱 - 质谱法，MeIQx（4纳摩尔/毫摩尔肌酸（酐））是主要产生的诱变剂，同时还产生少量的DiMeIQx，包括4,8 - 和7,8 - 二甲基咪唑并喹喔啉。在高效液相色谱上还分离出了其他一些诱变峰，但未对其进行鉴定。改变单糖和二糖的浓度（0 - 2.4毫摩尔）和类型对所有诱变化合物的产率有很大影响。摩尔量低于肌酸（酐）浓度的糖会提高产率，直至达到最佳值。在更高浓度下，所有诱变剂的形成均显著减少。葡萄糖、果糖、蔗糖和乳糖的情况相同，不过单糖的抑制作用最为明显。过量的糖对诱变化合物形成的抑制作用被认为是美拉德反应产物的作用，其可能通过攻击肌酸来阻断咪唑并喹喔啉的形成。表明随着葡萄糖浓度增加未反应肌酸回收率降低的数据以及添加典型美拉德反应产物5 - 羟甲基 - 2 - 糠醛后对这些诱变剂形成的抑制作用为这一机制提供了支持。
