Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma
Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma
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DOI：
10.1158/1055-9965.epi-06-0199
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发表时间：
2006-08-01
影响因子：
3.8
通讯作者：
Hecht, Stephen S.
中科院分区：
文献类型：
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作者：
Carmella, Steven G.;Yoder, Andrea;Hecht, Stephen S.
多环芳烃（PAH）和烟草特有的亚硝胺，例如4 -（甲基亚硝胺基）-1 -（3 -吡啶基）-1 -丁酮（NNK），被广泛认为是香烟烟雾中两类重要的肺癌致癌物。在本研究中，我们开发了一种方法，通过对吸烟者1毫升血浆中的r - 1，t - 2，3，c - 4 -四羟基-1，2，3，4 -四氢菲（PheT）和4 -（甲基亚硝胺基）-1 -（3 -吡啶基）-1 -丁醇（NNAL）进行定量，来估算个体对这些化合物的摄取量。PheT和NNAL分别是PAH和NNK摄取的生物标志物。将[D - 10]PheT和[吡啶 - D - 4]NNAL作为内标加入血浆。血浆用β - 葡糖醛酸糖苷酶处理，以释放任何结合的PheT和NNAL。分析物通过混合模式阳离子交换柱进行固相萃取富集，PheT组分通过高效液相色谱进一步纯化。适当的组分通过气相色谱 - 负离子化学电离 - 质谱法分析PheT，通过液相色谱 - 电喷雾电离 - 质谱法分析NNAL。该方法灵敏（定量限：PheT为13飞摩尔/毫升；NNAL为3飞摩尔/毫升）、准确且精密。16名吸烟者血浆中PheT和NNAL的水平平均分别为95 ± 71和36 ± 21飞摩尔/毫升，这与在尿液中发现的量的1%到2%相似。该方法在吸烟者致癌物摄取和肺癌的分子流行病学研究中应该是有用的。
Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely accepted to be two important types of lung carcinogens in cigarette smoke. In this study, we have developed a method to estimate individual uptake of these compounds by quantifying r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in 1 mL of smokers' plasma. PheT and NNAL are biomarkers of PAH and NNK uptake, respectively. [D-10]PheT and [pyridine-D-4]NNAL were added to plasma as internal standards. The plasma was treated with beta-glucuronidase to release any conjugated PheT and NNAL. The analytes were enriched by solid-phase extraction on a mixed mode cation exchange cartridge and the PheT fraction was further purified by high-performance liquid chromatography. The appropriate fractions were analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry for PheT and liquid chromatography-electrospray ionization-mass spectrometry for NNAL. The method was sensitive (limits of quantitation: PheT, 13 fmol/mL; NNAL, 3 fmol/mL), accurate, and precise. Levels of PheT and NNAL in plasma from 16 smokers averaged 95 +/- 71 and 36 +/- 21 fmol/mL, respectively, which are similar to 1% to 2% of the amounts found in urine. This method should be useful in molecular epidemiology studies of carcinogen uptake and lung cancer in smokers.