Wilp J, Zwickenpflug W, Richter E
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University, Nussbaumstrasse 26, D-80336, Munich, Germany.
Food Chem Toxicol. 2002 Aug;40(8):1223-8. doi: 10.1016/s0278-6915(02)00039-x.
The tobacco alkaloid myosmine was detected in nut and nut products [J. Agric. Food Chem. 46 (1998) 2703]. Upon nitrosation, myosmine yields 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and N-nitrosonornicotine (NNN) [J. Agric. Food Chem. 48 (2001) 392]. NNN is a strong oesophageal carcinogen in rats. Metabolic activation of NNN leads to formation of DNA and protein adducts which release HPB upon hydrolysis. In the present study the time, pH and dose-dependent nitrosation of myosmine and its covalent binding to DNA was investigated. [5-(3)H]myosmine was incubated with nitrite for 1-24 h in buffer solutions adjusted to pH 1-6. At pH 2-4 myosmine was easily nitrosated and gave rise to two major products, HPB and NNN, and five minor not yet identified products. Maximal formation was achieved for HPB at pH 2 after 8 h (72% of total radioactivity) and for NNN at pH 3 after 8 h (16%). For DNA binding studies labeled myosmine was incubated under nitrosation conditions with calf thymus DNA. Within 3 h up to 0.1% of the radioactivity was covalently bound to DNA. Endogenous nitrosation of myosmine, present in nuts and other dietary components could constitute a significant risk factor for tumours in the upper intestinal tract such as oesophageal adenocarcinoma, which are unrelated to tobacco smoking and alcohol abuse.
在坚果及坚果制品中检测到了烟草生物碱麦斯明（[《农业与食品化学杂志》46 (1998) 2703]）。麦斯明经亚硝化后会生成4-羟基-1-(3-吡啶基)-1-丁酮（HPB）和N-亚硝基去甲烟碱（NNN）[《农业与食品化学杂志》48 (2001) 392]。NNN是大鼠体内一种强效的食管致癌物。NNN的代谢活化会导致形成DNA和蛋白质加合物，这些加合物在水解时会释放出HPB。在本研究中，对麦斯明的亚硝化时间、pH值和剂量依赖性及其与DNA的共价结合进行了研究。将[5-(3)H]麦斯明与亚硝酸盐在pH值调至1 - 6的缓冲溶液中孵育1 - 24小时。在pH值为2 - 4时，麦斯明很容易被亚硝化，产生两种主要产物HPB和NNN，以及五种尚未鉴定的次要产物。8小时后，在pH值为2时HPB的生成量达到最大（占总放射性的72%），在pH值为3时NNN的生成量在8小时后达到最大（16%）。对于DNA结合研究，将标记的麦斯明在亚硝化条件下与小牛胸腺DNA一起孵育。在3小时内，高达0.1%的放射性与DNA共价结合。存在于坚果和其他饮食成分中的麦斯明的内源性亚硝化可能是上消化道肿瘤（如食管腺癌）的一个重要风险因素，这些肿瘤与吸烟和酗酒无关。
