Abstract：
Several aromatic amines (AA) are classified as human carcinogens, and tobacco smoke is one of the main sources of exposure. Once in the human body, they undergo different metabolic pathways which lead to either their excretion or ultimately to the formation of DNA and protein adducts. The aim of this study was to investigate AA in 68 urine samples (aged 29-79, 47% female), including 10 smokers (S), 28 past-smokers (PS) and 30 never-smokers (NS), and to study if there was a relation between the smoking status and the amount of the AA present. GCxGC-MS was used to analyze AA in complex urine samples due to its high peak capacity and the fact that it provides two sets of retention times and structural information, which facilitates the separation and identification of the target analytes. First, a qualitative comparison of an example set of a NS, PS and S sample was carried out, in which 38, 45 and 46 AA, respectively, could be tentatively identified. Afterwards, seven AA were successfully quantified in the samples. Of these, 4-ethylaniline (4EA, p = 0.015), 2,4,6-trimethylaniline (2,4,6TMA, p = 0.030), 2-naphthylamine (2NA, p = 0.014) and the sum of 2,4- and 2,6-dimethylaniline (DMA, p = 0.017) were found in significantly different (α = 0.05) concentrations for the S, 29 ± 14, 87 ± 49, 41 ± 26, and 105 ± 57 ng/L respectively, compared to the NS, 15 ± 6, 42 ± 30, 16 ± 6, and 48 ± 28 ng/L. And 2,4,6TMA (39 ± 26, p = 0.022), 2NA (18 ± 9, p = 0.025) and DMA (53 ± 46, p = 0.030), were also found at significantly higher concentrations in samples from S when compared to PS. However, some samples had AA concentrations outside the calibration curve and could not be taken into account, especially for 2-methylaniline (2MA). Therefore, all the samples were evaluated using a quantitative screening approach, by which the intensities of 4EA (p = 0.019), 2,4,6TMA (p = 0.048), 2NA (p = 0.016), DMA (p = 0.019) and 2MA (p = 0.006) in S were found to be significantly (α = 0.05) higher than in the NS, and 2MA (p = 0.019) and 4EA (p = 0.023) in S were found to be significantly higher than in the PS. An association between the smoking status and the amount of certain AA present could therefore be found. This information could be used to study the relation between the smoking status, the amount of AA present, and smoking related diseases like bladder cancer.
摘要：
几种芳香胺（AA）被归类为人类致癌物，烟草烟雾是主要的暴露源之一。一旦进入人体，它们经历不同的代谢途径，导致它们的排泄或最终形成DNA和蛋白质加合物。这项研究的目的是调查68个尿液样本中的AA（年龄29-79岁，女性占47％），包括10名吸烟者（S），28名过去吸烟者(PS)和30名从未吸烟者(NS)，并研究吸烟状况与存在的AA量之间是否存在关系。GCxGC-MS用于分析复杂尿液样品中的AA，因为它具有较高的峰容量，并且它提供了两组保留时间和结构信息，这有利于目标分析物的分离和鉴定。首先,NS示例集的定性比较，进行PS和S样品，其中38、45和46AA，分别,可以暂时确定。之后,在样品中成功定量了7个AA。其中,4-乙基苯胺（4EA，p=0.015),2,4,6-三甲基苯胺(2,4,6TMA，p=0.030),2-萘胺(2NA,p=0.014)和2,4-和2,6-二甲基苯胺的总和(DMA，p=0.017）在S的显着不同（α=0.05）浓度中发现，分别为29±14、87±49、41±26和105±57ng/L，与NS相比，15±6、42±30、16±6和48±28ng/L和2,4,6TMA（39±26，p=0.022），2NA（18±9，p=0.025）和DMA（53±46，p=0.030），与PS相比，在来自S的样品中也发现了明显更高的浓度。然而,一些样品的AA浓度超出校准曲线，不能考虑在内，特别是2-甲基苯胺（2MA）。因此,所有样本都使用定量筛选方法进行评估，其中4EA的强度(p=0.019)，2,4,6TMA（p=0.048），2NA（p=0.016），发现S中的DMA（p=0.019）和2MA（p=0.006）明显高于NS中的（α=0.05），发现S中的2MA（p=0.019）和4EA（p=0.023）显着高于PS。因此，可以发现吸烟状况与某些AA含量之间的关联。这些信息可以用来研究吸烟状况之间的关系，存在的AA的数量，和吸烟相关的疾病，如膀胱癌。
