Murphy S E, Carmella S G, Idris A M, Hoffmann D
American Health Foundation, Valhalla, New York 10595.
Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):423-8.
It was recently reported that toombak, a type of snuff used in the Sudan, contained unusually high levels of tobacco-specific nitrosamines. To estimate the internal dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) received by individuals who use this type of tobacco, urine from a group of users was analyzed for 2 metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide, NNAL-Gluc. NNK is a strong lung carcinogen believed to contribute to human lung cancer. NNAL is also a lung carcinogen. NNAL and NNAL-Gluc were analyzed by gas chromatography with a nitrosamine selective detector. The average levels detected were 0.39 +/- 0.14 (SD) nmol/ml urine (n = 7) and 0.88 +/- 0.50 nmol/ml urine (n = 7), respectively. In a 24-h period, these individuals would excrete from 0.12 to 0.44 mg of these two metabolites (expressed per mg NNAL). Therefore, assuming chronic toombak use, the minimum daily dose of NNK to which these users were exposed was 0.12-0.44 mg. This is the highest documented uptake of a nonoccupational carcinogen. Two diastereomers of NNAL-Gluc were present in all urine samples analyzed. Previously, these two diastereomers were identified in the urine of an NNK-treated patas monkey but only one was detected in the urine of NNK-treated rats. The level of the 4-hydroxy-1-(3-pyridyl)-1-butanone releasing hemoglobin adduct was also quantified in these individuals. This adduct is believed to be a measure of NNK activation. The levels ranged from 68 to 323 fmol/g hemoglobin [mean, 148 +/- 104 (SD)]. The wide range of adduct levels which were observed suggests that despite similar levels of NNK exposure, there are significant differences in the ability of individuals in this population to activate NNK, as well as potential differences in their cancer risk.
最近有报道称，苏丹使用的一种鼻烟toombak含有异常高含量的烟草特异性亚硝胺。为了估计使用此类烟草的个体摄入的4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）的体内剂量，对一组使用者的尿液进行了分析，检测NNK的两种代谢产物，4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）及其O-葡萄糖醛酸苷NNAL-Gluc。NNK是一种强烈的肺癌致癌物，被认为与人类肺癌有关。NNAL也是一种肺癌致癌物。采用带有亚硝胺选择性检测器的气相色谱法对NNAL和NNAL-Gluc进行分析。检测到的平均水平分别为0.39±0.14（标准差）nmol/ml尿液（n = 7）和0.88±0.50 nmol/ml尿液（n = 7）。在24小时内，这些个体将排泄出0.12至0.44毫克的这两种代谢产物（以每毫克NNAL表示）。因此，假设长期使用toombak，这些使用者接触的NNK最低日剂量为0.12 - 0.44毫克。这是有记录的非职业性致癌物的最高摄入量。在所有分析的尿液样本中均存在NNAL-Gluc的两种非对映异构体。此前，在经NNK处理的粗尾猿尿液中鉴定出了这两种非对映异构体，但在经NNK处理的大鼠尿液中仅检测到一种。还对这些个体中释放血红蛋白加合物的4-羟基-1-（3-吡啶基）-1-丁酮水平进行了定量。这种加合物被认为是NNK活化的一种度量。其水平范围为68至323 fmol/g血红蛋白[平均值，148±104（标准差）]。观察到的加合物水平范围很广，这表明尽管NNK暴露水平相似，但该人群中个体活化NNK的能力存在显著差异，以及他们患癌风险的潜在差异。
