Melikian Assieh A, Djordjevic Mirjana V, Chen Shuquan, Richie John, Stellman Steven D
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1408-15. doi: 10.1158/1055-9965.EPI-06-1097.
Urinary metabolites of tobacco smoke toxins are often used as biomarkers for the evaluation of active and passive exposure to cigarette smoke toxins. In a study of healthy smokers, we investigated concentrations of urinary biomarkers in relation to concentrations of selected toxins in mainstream cigarette smoke as determined by machine smoking of cigarettes in a manner that mimics an individual's smoking behavior (topography). Concentrations of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and benzo(a)pyrene, in mainstream smoke determined under human smoking conditions, and their urinary metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and 1-hydroxypyrene were established for 257 individuals who smoked low-yield (0.1-0.8 mg Federal Trade Commission nicotine/cigarette; mean, 0.66; n = 87), medium-yield (0.9-1.2 mg nicotine/cigarette; mean, 1.1; n = 109), and high-yield cigarettes (nicotine, >1.3 mg nicotine/cigarette; mean, 1.41; n = 61). Levels of urinary metabolites expressed per unit of delivered parent compounds decreased with increased smoke emissions. In smokers of low-, medium-, and high-yield cigarettes, the respective cotinine (ng/mg creatinine)-to-nicotine (mg/d) ratios were 89.4, 77.8, and 57.1 (low versus high; P = 0.06); the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (pmol/mg creatinine)-to-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (ng/d) ratios were 0.81, 0.55, and 0.57 (low versus high; P = 0.05); and the 1-hydroxypyrene (pg/mg creatinine)-to-benzo(a)pyrene (ng/d) ratios were 1.55, 1.13, and 0.97 (low versus high; P = 0.008). Similarly, means of cotinine per unit of delivered nicotine in smokers who consumed <20 cigarettes per day was 3.5-fold higher than in those who smoked >20 cigarettes per day. Likewise, a negative correlation was observed between cotinine-to-nicotine ratios and delivered doses of nicotine in subgroups of smokers who used the identical brand of cigarette, namely a filter tip-vented Marlboro (r = -0.59), which is a popular brand among Euro-Americans, and Newport (r = -0.37), a menthol-flavored cigarette without filter tip vents that is preferred by African-Americans. Thus, the intensity of the exposures significantly affects the levels of urinary biomarkers of exposure and should be taken into account in the evaluation of human exposure to cigarette smoke toxins.
烟草烟雾毒素的尿液代谢物常被用作生物标志物，以评估主动和被动接触香烟烟雾毒素的情况。在一项针对健康吸烟者的研究中，我们调查了尿液生物标志物的浓度与主流香烟烟雾中选定毒素浓度之间的关系，这些毒素浓度是通过模拟个体吸烟行为（抽吸模式）的机器抽吸香烟来测定的。在人类吸烟条件下测定的主流烟雾中尼古丁、4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮和苯并（a）芘的浓度，以及它们的尿液代谢物可替宁、4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇和1-羟基芘的浓度，在257名吸低焦油（0.1 - 0.8毫克联邦贸易委员会尼古丁/支香烟；平均0.66；n = 87）、中焦油（0.9 - 1.2毫克尼古丁/支香烟；平均1.1；n = 109）和高焦油香烟（尼古丁含量>1.3毫克尼古丁/支香烟；平均1.41；n = 61）的个体中得以确定。每单位递送母体化合物的尿液代谢物水平随烟雾排放量增加而降低。在吸低、中、高焦油香烟的吸烟者中，各自的可替宁（纳克/毫克肌酐）与尼古丁（毫克/天）的比值分别为89.4、77.8和57.1（低焦油与高焦油相比；P = 0.06）；4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（皮摩尔/毫克肌酐）与4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（纳克/天）的比值分别为0.81、0.55和0.57（低焦油与高焦油相比；P = 0.05）；1-羟基芘（皮克/毫克肌酐）与苯并（a）芘（纳克/天）的比值分别为1.55、1.13和0.97（低焦油与高焦油相比；P = 0.008）。同样，每天吸食<20支香烟的吸烟者中，每单位递送尼古丁的可替宁平均值比每天吸食>20支香烟的吸烟者高3.5倍。同样，在使用相同品牌香烟的吸烟者亚组中，可替宁与尼古丁的比值和递送的尼古丁剂量之间存在负相关，即滤嘴有通风孔的万宝路（r = -0.59），这是欧美人群中受欢迎的品牌，以及薄荷味无滤嘴通风孔的新港（r = -0.37），这是非洲裔美国人喜欢的品牌。因此，接触强度显著影响接触的尿液生物标志物水平，在评估人类接触香烟烟雾毒素时应予以考虑。
