Characteristic Analysis Of N-nitrosamines Exposure In High Incidence Area Of Esophageal Cancer

Objective:1.A method based on gas chromatograph-mass spectrometry(GC-MS)was developed and optimized to investigate nine N-nitrosamines in the drinking water and urine.2.To explore the characteristics of the target analytes exposure in drinking water and urine in the city of Nanjing and Huai'an.3.To evaluate a possible correlationship between N-nitrosamines exposure and esophageal cancer.Methods:1.Solid-phase extraction were used to extract N-nitrosodimethylamine(NDMA),N-nitrosodiethylamine(NDEA),N-nitrosomethylethylamine(NMEA),N-nitrosodipropylamine(N DPA),N-nitrosodibutylamine(NDBA),N-nitrosopiperidine(NPip),N-nitrosopyrrolidine(NPyr),N-nitrosomorpholine(NMor),N-nitrosodiphenylamine(NDphA)in drinking water and human urine.Samples were analyzed by using GC-MS after pretreatment and then a quantitative method was established for each analyte.2.20 sampels of source water and finished water were collected from five waterplants in Nanjing city in March 2017.In April 2017,28 samples of source water and finished water of nine waterplants were collected from in Hongze County,Jinhu County and Xuyi County in Huai'an.Solid phase extraction-gas chromatography-mass spectrometry were used to detect and analyze the exposure characteristics of nine N-nitrosamines in drinking water in Nanjing and Huai'an.3.202 urine samples were collected from physical examination people in Nanjing Occupational Disease Prevention and Control whose ages ranged from 20-75 in April 2017.Meanwhile,72 urine samples were collected from the high incidence area of esophageal cancer of Tongxi village in Hongze County,Huai'an whose ages ranged from 40-75 in May 2017.Wilcoxon rank sum test was employed to compare the differences inconcentrations of nine N-nitrosamines levels between the high and low incidence area of esophageal cancer,then explore the relationship between exposure of N-nitrosamines and esophageal cancer.Results:1.The calibration curves showed good linearity within the range 10-1000 ?g/L for the nine N-nitrosamines.Limit of detection of method(MDL)for the nine N-nitrosamines in drinking water were2.3-6.4 ng/L,and 0.3-0.6?g/L in urine.The recovery in drinking water ranged from 62.3%-109.7%,and 80.1%-115.0%in urine.Both the intra-day and inter-day precision wereless than 10%.2.Except for the NMEA,the detected concentration of the other eight N-nitrosamines were 0.7-58.3 ng/L in source water and finished water of waterplants in Nanjing and Huai'an.The detection rate of NDPA and NDBA was the highest,meanwhile the concentration of them and total nitrosamines in drinking water in Huai'an area were higher than which in Nanjing area.3.NDMA,NDPA,NDBA,NPyr,NMor,NDphA were detected in the low incidence area.The detection rate of NDPA,NPyr and NMor was above 90%.In the high incidence area of esophageal cancer,the detection rate of NDMA,NDPA and NMor were 36.1%,100%and 100%,respectively.The maximum concentration of NDMA was 4746.2ng/L,while the concentration of total nitrosamines was 4073.5-50467.6 ng/L in the high incidence area of esophageal cancer.There were significant differences(P<0.05)in NDMA,NDPA,NDBA,NPip,NMor,NDphA and total nitrosamines levels between the high and low incidence area of esophageal cancer.Conclusion:A SPE-GC-MS method was developed and optimized to analyze the nine N-nitrosamines in drinking water and human urine.The method was validated to be precise,sensitive,and accurate in this study.It can be applied to the evaluation of exposure of the nine N-nitrosamines.N-nitrosamineswere detected in the source water and finished water of waterplants in Nanjing and Huai'an.The people in the high and low incidence area of esophageal cancer were generally exposed to N-nitrosodimethylamine(NDMA),N-nitrosodipropylamine(NDPA),N-nitrosodibutylamine(NDBA),N-nitrosopiperidine9(NPip),N-nitrosopyrrolidine(NPyr),N-nitrosomorpholine(NMor)andN-nitrosodiphenylamine(NDphA).The detection rate of NDMA,NDPA,NPyr and NMor in Huai'an were higher than those in Nanjing.The difference of exposure of N-nitrosamines in urine of the high and low incidence area of esophageal cancer was statistically significant,which provided the basis for further study of the relationship between nitrosamines and esophageal cancer.