| Cancer is a disease caused by the loss of normal regulation and unlimited proliferation of cells.Affected by excessive unhealthy diet,gradual deterioration of the environment,serious aging and other factors,the incidence of cancer is increasing worldwide,and it has become the most threatening disease to human health.Aflatoxin(AFT)is a highly toxic isofuran ring carcinogen.The infection of aflatoxin to various oil crops and oil products has caused great harm to human health.However,the specific harm degree and pathogenesis of AFT to humans are still unclear.In the first part of this paper,455 residents in eastern Shandong,China were selected as the subjects,and their dietary intake was statistically analyzed by online questionnaire.Probabilistic assessment and point assessment were used to study the carcinogenic risk of AFT from the perspective of dietary exposure.In the second part of this thesis,the molecular dynamics simulation(MD)method was used to discuss the possible action mechanism of AFT.In the third part of this thesis,the specific reasons for the effects of AFT on the normal physiological activities of DNA helicases and polymerases were investigated by stretching kinetics and hole analysis.The dietary exposure risk of residents living in eastern Shandong province was assessed by establishing a My SQL database on the concentration of AFT in processed food in China and collecting the dietary intake questionnaire of residents living in eastern Shandong Province.Two dietary exposure risk assessment methods,point assessment and probability assessment,were used to assess the dietary exposure risk of the residents living in eastern Shandong province.The results showed that the concentrations of AFT in corn,peanut and their products were 21.08 μg/kg and 6.61 μg/kg,respectively.The two risk exposure indicators,namely margin of exposure(MOE)and incremental lifetime Cancer risk(ILCR),were 25765 and2.61×10-6,respectively.This indicated that the dietary exposure to AFT was within the safe range.In the population of eastern Shandong province,the risk of AFT exposure was higher in female/college educated/unemployed population than in male/graduate educated/employed population.Comparison of the data from molecular dynamics simulations revealed that AFT insertion in DNA base pairs in a non-covalent manner severely deforms normal DNA,whereas enhancedπ-π interactions result in a pronounced inhibition of DNA unfolding.In addition,AFT has a high steric hindrance,which has a great detrimental effect on the proper work of DNA semireserved replication-related enzymes.Bacillus fragment I(BF)is an excellent tool for DNA polymerase research.The BF＿DNA＿AFT complex system was studied by stretching kinetics and hole analysis.The covalent binding of AFT increases the width of the double-stranded DNA and prevents it from crossing the active pore of the polymerase,thereby inhibiting the normal biological activity of the polymerase.The results of the binding free energy calculation also showed that the binding ability of DNA to helicase was significantly weakened after AFT binding,indicating that the introduction of AFT also greatly affected the normal binding of DNA to helicase.This study not only discussed the dietary exposure,risk assessment and possible toxicity mechanism of AFT in eastern Shandong,China,but also provided a reference for food safety and reasonable diet in the future,which would play a role in food safety in China and the world. |
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