Investigation Of The Effects Of Heavy Metal Ions And Quercetin On NDMA Formation In Simulated Gastric Fluid

N-nitrosodimethylamine (NDMA) is the simplest N-nitroso compound (NOC) instructure, but it is one of the most carcinogenic speices among the NOCs.International Agency for Research on Cancer (IARC) classified NDMA and threeother NOCs as carcinogens of the category2A. It was reported that exposure toNDMA could occur exogenously and endogenously. Moreover, the amount ofendogenous NDMA formation is about60%of the total exposure of NDMA.Therefore, the studies of the endogenous NDMA formation and inhibition areimportant research contents.Heavy metals as pollutants have caused severe threats to the environment andhuman. Quercetin is recognized as an important natural herbal ingredient. However,few studies about the effects of heavy metals and quercetin on endogenous NDMAformation have been done in the literature. Therefore, the subjects of this thesis are toinvestigate the effects of heavy metal ions and quercetin on endogenous NDMAformation. The main contents of this thesis are as the following parts:1. Reaction system and detection methods of the endogenous NDMA formationStrong acidic environment in the stomach has been considered to be one of themost important organs where endogenous N-nitroso compounds form. Therefore, theformation of NDMA in the simulated gastric fluid was selected in this paper tomimick the endogenous NDMA formation. The establishment of the simulated gastricfluid reaction system of NDMA formation includes: selecting the component and theirproportion of the simulated gastric fluid and determining the concentration of NDMAprecursors and the reaction conditions. Analysis and detection method of NDMA isthe mature SPE-GC/MS method established by our group. In the studies of themechanism, ion chromatography was used to track the concentration changes of twoprecursors of NDMA.2. The effect and mechnaism of heavy metal ions on NDMA formation insimulated gastric fluid (SGF)Cadmium, mercury and lead, which have been the most widespread heavy metalpollutants in our country and have caused severe threats to human health, wereselected as the research object in this thesis. The results indicate that, in the simulatedgastric fluid, Cd(II), Hg(II) and Pb(II) ions can promote the formation of NDMA, and the biggest promotion rates of them were19.9%,27.9%and13.8%. It is worthy tonote that Pb(II) at the concentration of0.005mg/L, which already met the guidelinevalues in food and drinking water, still promotes NDMA formation by about14%.The results from the ion chromatography indicate that there are stronger interactionsbetween the heavy metal ions and DMA than that between heavy metal ions andnitrite. It infers that heavy metal ions may react with DMA to form an activatedintermediate, which leads to the more yield of NDMA formation. The findings of thisstudy are helpful for understanding the mechanisms of heavy metal polluting theenvironment and playing an important role in keeping healthy.3. The inhibition effect of quercetin on NDMA formation in SGFAs an important natural herbal ingredient, quercetin has antioxidant, anti freeradicals, anti-cancer and other physiological functions, and it is also a potentialinhibitor of NDMA formation. In the simulated gastric fluid, two concentrations ofwater soluble quercetin,0.01and0.1mg/mL, were selected and the results indicatethat quercetin at these two levels can both promote the formation of NDMA. Thesame concentrations of vitamin C were chosen to do experiments for comparison, andthe results also indicate that Vc can promote the formation of NDMA. Increasing theconcentration up to1mg/mL, it can significantly inhibit the formation of NDMA andthe inhibition rate reached42.9%. Unfortunately, due to the limited amount of watersoluble quercetin, the experiment was unable to complete with the presence of1mg/mL. The results indicate that a relatively high concentration of Vc has aninhibitory effect. In addition, the results on the commercially available quercetinindicate that ethanol solvent inhibits the formation of NDMA, and the inhibitory rateincreases with increasing its concentration, and the inhibition rate of10%ethanolreaches about80%. The results are helpful for reducing endogenous NDMAformation and maintaining human health.