Experimental and Theoretical Investigation of Effects of Ethanol and Acetic Acid on Carcinogenic NDMA Formation in Simulated Gastric Fluid.
N-nitrosodimethylamine (NDMA), as a representative of endogenously formed N-nitroso compounds (NOCs), has become the focus of considerable research interest due to its unusually high carcinogenicity. In this study, effects of ethanol and acetic acid on the formation of NDMA from dimethylamine (DMA) and nitrite in simulated gastric fluid (SGF) were investigated. Experimental results showed that ethanol in the concentrations of 1-8% (v/v) and acetic acid in the concentrations of 0.01-8% (v/v) exhibit inhibitory and promotion effects on the formation of NDMA, respectively. Moreover, they are both in a dose-dependent manner with the largest inhibition/promotion rate reaching ∼70%. Further experimental investigations indicate that ethanol and acetic acid are both able to scavenge nitrite in SGF. It implies that there are interactions of ethanol and acetic acid with nitrite or nitrite-related nitrosating agents rather than DMA. Theoretical calculations confirm the above experimental results and demonstrate that ethanol and acetic acid can both react with nitrite-related nitrosating agents to produce ethyl nitrite (EtONO) and acetyl nitrite (AcONO), respectively. Furthermore, the reactivities of ethyl nitrite, acetyl nitrite, and dinitrogen trioxide reacting with DMA were found in the order of AcONO > N2O3 ≫ EtONO. This is probably the main reason why there are completely different effects of ethanol and acetic acid on NDMA formation. On the basis of the above results, two requirements for a potential inhibitor of NOCs formation in SGF were provided. The results obtained in this study will be helpful in better understanding the inhibition/promotion mechanisms of compounds on NDMA formation in SGF and searching for protective substances to prevent carcinogenic NOCs formation.
College of Life Science & Bioengineering, Beijing University of Technology , Beijing 100124, P. R. China.
Ou
O
Zhang
Department of Stomatology, Chinese PLA 307 Hospital, Academy of Military Medical Sciences , Beijing, 100071, P. R. China.
Xuan
X
Zou
Department of Stomatology, Chinese PLA 307 Hospital, Academy of Military Medical Sciences , Beijing, 100071, P. R. China.
Qi-Hong
QH
Li
College of Life Science & Bioengineering, Beijing University of Technology , Beijing 100124, P. R. China.
Zhi
Z
Sun
College of Life Science & Bioengineering, Beijing University of Technology , Beijing 100124, P. R. China.
Yong Dong
YD
Liu
College of Life Science & Bioengineering, Beijing University of Technology , Beijing 100124, P. R. China.
Ru Gang
RG
Zhong
D019342:Acetic Acid / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D001826:Body Fluids / Q000378:metabolism*; D002273:Carcinogens / Q000737:chemistry* / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000737:chemistry* / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013270:Stomach
D002273:Carcinogens; D000431:Ethanol; D004128:Dimethylnitrosamine; D019342:Acetic Acid