Takanashi H, Homma H, Matsui M
Kyoritsu College of Pharmacy, Tokyo, Japan.
Chem Biol Interact. 1988;66(1-2):49-59. doi: 10.1016/0009-2797(88)90040-3.
N-Nitrosodiethylamine (NEN) and N-nitrodiethylamine (NEA) are carcinogens and in vitro activators of hepatic UDP-glucuronosyltransferase (GT) toward 2-aminophenol (AP) and 4-nitrophenol (NP). In this communication, they were intraperitoneally administered to male Wistar rats for 7 days and GT activities were determined towards AP, NP, phenolphthalein (PH) and testosterone (TS). Administration of 30 or 20 mg/kg dose of NEN caused marked decrease of liver and body weights, and did not affect hepatic GT activities. Injection of 10 mg/kg dose of NEN did not diminish liver and body weights, and increased the maximally activated GT activities toward AP and NP. In contrast, 30 mg/kg dose of NEA, did not affect either liver and body weights or GT activities. N-Nitrosodimethylamine (NMN), which is a carcinogen and a weak in vitro AP GT activator, was more toxic than NEN, and 3.6 mg/kg dose of NMN appears to induce GT toward NP and AP. Administration of 46.5 mg/kg N-nitrosodibutylamine (NBN), which is a carcinogen but not a GT activator, did not affect GT activities or liver body weights.
N-亚硝基二乙胺(NEN)和N-硝基二乙胺(NEA)是致癌物,也是肝脏尿苷二磷酸葡萄糖醛酸基转移酶(GT)对2-氨基酚(AP)和4-硝基苯酚(NP)的体外激活剂。在本报告中,将它们腹腔注射给雄性Wistar大鼠7天,并测定了GT对AP、NP、酚酞(PH)和睾酮(TS)的活性。给予30或20mg/kg剂量的NEN会导致肝脏和体重显著下降,且不影响肝脏GT活性。注射10mg/kg剂量的NEN不会减少肝脏和体重,反而会增加GT对AP和NP的最大激活活性。相比之下,30mg/kg剂量的NEA对肝脏和体重以及GT活性均无影响。N-亚硝基二甲胺(NMN)是一种致癌物,也是一种体外AP GT弱激活剂,其毒性比NEN更大,3.6mg/kg剂量的NMN似乎会诱导GT对NP和AP的活性。给予46.5mg/kg N-亚硝基二丁胺(NBN),它是一种致癌物但不是GT激活剂,对GT活性或肝脏体重没有影响。