Biomonitoring of urinary cotinine concentrations associated with plasma levels of nicotine metabolites after daily cigarette smoking in a male Japanese population.

Biomonitoring of urinary cotinine concentrations associated with plasma levels of nicotine metabolites after daily cigarette smoking in a male Japanese population.
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DOI:
10.3390/ijerph7072953
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发表时间:
2010-07
影响因子:
--
通讯作者:
Yamazaki H
Yamazaki H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nagano T;Shimizu M;Kiyotani K;Kamataki T;Takano R;Murayama N;Shono F;Yamazaki H

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在92名平均年龄为37岁、平均每天吸烟23支、持续16年的日本男性吸烟者中,每日吸烟后对尼古丁、可替宁和3′-羟基可替宁的血浆和尿液水平进行人体生物监测。对人群成员进行尼古丁代谢酶细胞色素P450 2A 6(CYP 2A 6)基因分型。在每日吸烟条件下,受试者在采样日吸第一支烟后1小时的尼古丁平均水平、其代谢物可替宁和3′-羟基可替宁水平以及这三种水平的总和分别为血浆20.1、158、27.7和198 ng/mL,尿液846、1,020、1,010和2,870 ng/mL。3′-羟基可替宁的血浆水平以及尼古丁和3′-羟基可替宁的尿液水平取决于CYP 2A 6表型组,该表型组是根据受试者的CYP 2A 6基因型估计的,包括全基因缺失的受试者。血浆可替宁水平与采样前一天吸烟数(r = 0.71)、平均每日吸烟数(r = 0.58)和Brinkman指数(每日吸烟数×年数,r = 0.48)显著相关。血浆中尼古丁、可替宁和3′-羟基可替宁浓度之和与血浆可替宁水平具有相似的关系。可替宁的尿浓度和尼古丁代谢物浓度的总和也显示出与血浆水平和前一天的平均吸烟量显着相关。通过测量尿可替宁浓度并使用由上述数据导出的线性回归方程,预测两名自报轻度吸烟习惯的受试者每天吸烟的数量。这些结果表明,尿可替宁浓度的生物监测是吸烟者血浆可替宁水平和尼古丁代谢产物总和的良好、易用的标志物,与CYP 2A 6的遗传多态性无关。
Human biomonitoring of plasma and urinary levels of nicotine, cotinine, and 3′-hydroxycotinine was conducted after daily cigarette smoking in a population of 92 male Japanese smokers with a mean age of 37 years who had smoked an average of 23 cigarettes per day for 16 years. Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). The mean levels of nicotine, the levels of its metabolites cotinine and 3′-hydroxycotinine, and the sum of these three levels in subjects one hour after smoking the first cigarette on the sampling day were 20.1, 158, 27.7, and 198 ng/mL in plasma and 846, 1,020, 1,010, and 2,870 ng/mL in urine under daily smoking conditions. Plasma levels of 3′-hydroxycotinine and urinary levels of nicotine and 3′-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Plasma cotinine levels were significantly correlated with the number of cigarettes smoked on the day before sampling (r = 0.71), the average number of cigarettes smoked daily (r = 0.58), and the Brinkman index (daily cigarettes × years, r = 0.48) under the present conditions. The sum of nicotine, cotinine, and 3′-hydroxycotinine concentrations in plasma showed a similar relationship to that of the plasma cotinine levels. Urinary concentrations of cotinine and the sum of nicotine metabolite concentrations also showed significant correlations with the plasma levels and the previous day’s and average cigarette consumption. The numbers of cigarettes smoked per day by two subjects with self-reported light smoking habits were predicted by measuring the urinary cotinine concentrations and using linear regression equations derived from above-mentioned data. These results indicate that biomonitoring of the urinary cotinine concentration is a good, easy-to-use marker for plasma levels of cotinine and the sum of nicotine metabolites in smokers independent of genetic polymorphism of CYP2A6.
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