Mori Y, Takahashi H, Yamazaki H, Toyoshi K, Obara T, Makino T, Nakae D, Takahashi S, Konishi Y
IARC Sci Publ. 1984(57):411-6.
The metabolic fate of the lung carcinogen N-nitrosobis(2-hydroxypropyl)amine (ND2HPA) in male Wistar rats was studied. The blood level after a single intraperitoneal (i.p.) injection of [1-14C]-ND2HPA at a dose of 3 g/kg body weight reached a maximum within 1 h. Most of the administered 14C was eliminated via the urine; 90.8% of the 14C was excreted in urine within 24 h, 5.5% in faeces, and 3.2% in expired air. About 11% of the 14C was detected in bile collected over 24 h. A relatively high concentration of 14C was found in the blood and target organs, such as the lung, liver, thyroid gland and kidney 1 h after treatment. Analysis by high-pressure liquid chromatography showed that the 14C in the blood and urine was mostly accounted for by unchanged ND2HPA, together with smaller amounts of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (N2HP2OPA). ND2HPA and N2HP2OPA were also detected in the lung and liver of rats 30 min to 12 h after the administration and were present in higher concentrations in the blood and lung than in the liver and pancreas. Besides ND2HPA and N2HP2OPA. N-nitrosomethyl(2-hydroxypropyl)amine (NM2HPA) was also found in urine collected over 6 h. ND2HPA, N2HP2OPA and NM2HPA showed mutagenicity in the Salmonella assay system with metabolic activation by a 9000 X g supernatant of rat liver, and N2HP2OPA was also mutagenic in the presence of a rat lung preparation. These data suggest that N2HP2OPA and NM2HPA might be important intermediates in the metabolic activation of ND2HPA to its ultimate carcinogenic form in rats.
研究了肺癌致癌物N-亚硝基双（2-羟丙基）胺（ND2HPA）在雄性Wistar大鼠体内的代谢命运。以3 g/kg体重的剂量单次腹腔注射[1-14C]-ND2HPA后，血液水平在1小时内达到峰值。大部分给予的14C通过尿液排出；24小时内90.8%的14C经尿液排出，5.5%经粪便排出，3.2%经呼出气体排出。在24小时内收集的胆汁中检测到约11%的14C。处理后1小时，在血液和靶器官如肺、肝、甲状腺和肾中发现了相对较高浓度的14C。高压液相色谱分析表明，血液和尿液中的14C主要由未变化的ND2HPA以及少量的N-亚硝基-（2-羟丙基）（2-氧代丙基）胺（N2HP2OPA）构成。给药后30分钟至12小时，在大鼠的肺和肝中也检测到了ND2HPA和N2HP2OPA，且血液和肺中的浓度高于肝和胰腺。除了ND2HPA和N2HP2OPA，在6小时内收集的尿液中还发现了N-亚硝基甲基（2-羟丙基）胺（NM2HPA）。在大鼠肝脏9000 X g上清液代谢活化的沙门氏菌检测系统中，ND2HPA、N2HP2OPA和NM2HPA均表现出致突变性，并且在大鼠肺制剂存在的情况下，N2HP2OPA也具有致突变性。这些数据表明，N2HP2OPA和NM2HPA可能是ND2HPA在大鼠体内代谢活化为最终致癌形式的重要中间体。
