Atawodi S E, Michelsen K, Richter E
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Germany.
Arch Toxicol. 1994;69(1):14-7. doi: 10.1007/s002040050130.
Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)butl-yl]-beta-O-d-glucosidu ronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2 +/- 3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6 +/- 1.7%) and its alpha-hydroxylation (11.5 +/- 2.2%) and N-oxidation (3.6 +/- 1.6%) products. The presence of alpha-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates.
除了4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）外，[4-（甲基亚硝胺基）-1-（3-吡啶基）丁基]-β-O-D-葡萄糖醛酸（NNAL-Glu）是烟草特异性亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）的另一种重要代谢产物，已在烟草使用者和大量接触侧流香烟烟雾的非吸烟者的尿液中检测到。为了评估NNAL-Glu形成和排泄的毒理学意义，研究了[5-³H]-NNAL-Glu在大鼠体内的代谢。五只雄性F344大鼠通过静脉注射给予3.7mg/kg的[5-³H]-NNAL-Glu，并通过高效液相色谱法分析尿液中的代谢产物。超过90%的放射性在最初24小时内随尿液排出。未变化的NNAL-Glu占总放射性的81.2±3.1%；其余部分的剂量似乎发生了去结合作用，导致NNAL（3.6±1.7%）及其α-羟基化产物（11.5±2.2%）和N-氧化产物（3.6±1.6%）经尿液排泄。尿液中存在NNAL-Glu的α-羟基化产物表明，这种NNK代谢产物可能在体内被激活为致癌中间体。
