Prokopczyk B, Brunnemann K D, Bertinato P, Hoffmann D
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595.
IARC Sci Publ. 1987(84):470-3.
N-(Nitrosomethylamino)propionitrile (NMAP) was isolated and identified in the saliva of betel-quid chewers in amounts ranging from 0.5 to 11.4 micrograms/l. Groups of 21 male and 21 female rats were given 60 subcutaneous injections of NMAP over a 20-week period (total doses, 0.055 and 0.23 mmol/rat). After 106 weeks, the higher dose had induced 18 (86%) malignant tumours of the nasal cavity in male and 15 (71%) in female rats. Nine (43%) liver tumours were observed among animals treated with the lower dose. Fischer 344 rats were treated with a single dose of NMAP (intravenously or subcutaneously, 0.4 mmol/kg; or by swabbing the oral cavity, 2.21 mmol/kg), and the levels of N7-methylguanine (7-meG) and O6-methylguanine (O6-meG) were measured in DNA isolated from oesophagus and nasal mucosa, which are target organs, and from liver which is not. Higher levels of O6-meG and 7-meG were detected in the nasal mucosa and lesser DNA methylation in the liver and oesophagus, independent of the mode of administration. This correlates with the results of the study of the tumorigenic properties of NMAP in rats.
在嚼槟榔者的唾液中分离并鉴定出了N-（亚硝基甲基氨基）丙腈（NMAP），其含量在0.5至11.4微克/升之间。将21只雄性和21只雌性大鼠分为几组，在20周内皮下注射60次NMAP（总剂量分别为0.055和0.23毫摩尔/只大鼠）。106周后，高剂量组在雄性大鼠中诱发了18个（86%）鼻腔恶性肿瘤，在雌性大鼠中诱发了15个（71%）。在低剂量处理的动物中观察到9个（43%）肝脏肿瘤。给Fischer 344大鼠单次注射NMAP（静脉注射或皮下注射，0.4毫摩尔/千克；或口腔涂抹，2.21毫摩尔/千克），并测量从作为靶器官的食管和鼻黏膜以及非靶器官肝脏中分离出的DNA中的N7-甲基鸟嘌呤（7-meG）和O6-甲基鸟嘌呤（O6-meG）水平。无论给药方式如何，在鼻黏膜中检测到较高水平的O6-meG和7-meG，而在肝脏和食管中检测到较低的DNA甲基化。这与NMAP对大鼠致癌特性的研究结果相关。
