丙烯酰胺(AA)是一种重要的食品内源污染物，与其体内环氧化代谢产物环氧丙酰胺(GA)均对人体健康具有潜在影响。项目组前期发现，大蒜素对AA及GA引起的毒性损伤具有明显的抑制效果，特别是在氧化应激、免疫、DNA损伤等方面作用尤为突出，但其作用机制尚不明确。通过基因芯片扫描显示，AA及GA对细胞凋亡、氧化损伤、癌症、免疫等相关基因产生明显的上调或下调作用，大蒜素是否通过影响这些基因的表达，进而缓解AA/GA引起的基因损伤呢？因此，本项目在此基础上，借助全基因组芯片表达谱、Real-time荧光定量PCR、Western-blot等技术对AA及GA致基因毒性靶基因进行筛选及验证；利用HPLC-MS/MS从加合物角度解释大蒜素作用机制；利用基因敲除、Western-blot、分子动力学模拟等方法从基因和蛋白水平共同验证大蒜素作用的分子机制，全面揭示大蒜素对AA及GA致基因损伤的干预机制及调控机理。

Acrylamide (AA) is an important endogenous contaminant in food, which has neurotoxic to human body, and has reproductive toxicity, genotoxicity and carcinogenicity to experimental animals. The in vivo metabolite glycidamide (GA) is more carcinogenicity, mutagenicity to experimentals animals. In our previous study, we found that allicin could significant reduce the damage induced by AA and GA, especially in oxidative stress, immune systems and DNA damage. But the mechanisms are not clear. Based on the results of genome microarray expression technology, we found that AA and GA had significant influence on the gene regarding to the cell death, oxidative damage, immune system process and cancers. Is it possible for allicin to relieve the gene damages induced by AA and GA through the expression of the corresponding genes? On the basis of the preliminary studies, the project aims to screen and verify the target genes of AA and GA induced genotoxicity based on the whole genome microarray expression technology, Real-time PCR and Western-blot technology, to analyze the change of adducts of hemoglobin and DNA by HPLC-MS/MS method, to explore the intevention mechanisms of allicin against AA and GA induced gene damage from gene and protein aspects based on gene silence technology, Western-blot and molecular dynamics simulations technology. These results can reveal the intevention mechanisms of allicin against AA and GA induced gene damages and lay the foundation to further develop and utilize allicin as a natural AA antidote, and meanwhile to provide the theory and new strategies to study the protective mechanisms of the other natural AA antidote.