Carcinogenicity of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, N-nitrosobis(2-hydroxypropyl)amine and cis-N-nitroso-2,6-dimethylmorpholine administered continuously in the Syrian hamster, and the effect of dietary protein on N-nitroso(2-hydroxypropyl)(2
Carcinogenicity of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, N-nitrosobis(2-hydroxypropyl)amine and cis-N-nitroso-2,6-dimethylmorpholine administered continuously in the Syrian hamster, and the effect of dietary protein on N-nitroso(2-hydroxypropyl)(2
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连续给予叙利亚仓鼠 N-亚硝基（2-羟丙基）（2-氧代丙基）胺、N-亚硝基双（2-羟丙基）胺和顺式-N-亚硝基-2,6-二甲基吗啉的致癌性以及饮食的影响
DOI：
10.1093/carcin/10.4.699
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发表时间：
1989
期刊：
影响因子：
4.7
通讯作者：
Scarpelli,DG
中科院分区：
文献类型：
--
作者：
Kokkinakis,DM;Scarpelli,DG
通过皮下注射法观察了三种胰腺癌致癌物N-亚硝基（2-羟丙基）（2-氧代丙基）胺（HPOP）、N-亚硝基双（2-羟丙基）胺（BHP）和顺式-N-亚硝基-2，6-二甲基吗啉（cis-NNDM）连续一周的作用。植入渗透泵，检查叙利亚仓鼠。在开始给药后25周，总剂量为220-250 mg/kg体重的HPOP诱导胰腺导管腺癌（41%）、肝脏胆管瘤（18%）和胆管癌（18%）。更高剂量的HPOP导致严重的肝损伤和增加的死亡率（LD 50 =280 mg/kg）Xis-NNDM和BHP的毒性低于HPOP，并且在950 mg/kg的剂量下诱导胰腺病变。这些数据证明，连续给药一周的HPOP诱导胰腺癌的时间表与涉及每周注射的时间表相比是有利的。应用该模型研究膳食蛋白在HPOP诱导的致癌性中的作用表明，在HPOP给药前2周，与8%蛋白质饮食相比，饲喂20%蛋白质饮食的动物胰腺中囊性、中间和管状复合体的数量显著较高。此外，胰腺癌和原位癌的发病率在低蛋白饮食的仓鼠中仅为13%，而在高蛋白饮食的仓鼠中为46%。
The effect of continuous week-long administration of the three pancreatic carcinogensN-nitroso(2-hydroxypropyl)(2-oxo-propyl)amine (HPOP),N-mtrosobis(2-hydroxypropyl)amine (BHP), andcis-N-nitroso-2,6-dimethylmorpholine (cis-NNDM), by a s.c. implanted osmotic pump, was examined in Syrian hamsters. HPOP at total doses of 220–250 mg/kg body weight induced ductal adenocarcinomas in the pancreas (41%), and cholangiomas (18%) and cholangiocarcinomas (18%) in the liver, 25 weeks following the initiation of treatment. Higher doses of HPOP resulted in severe hepatic injury and increased mortality (LD50=280 mg/kg).Cis-NNDM and BHP were less toxic than HPOP and induced pancreatic lesions at doses of 950 mg/kg. These data document that a week-long schedule of continuous administration of HPOP for the induction of pancreatic cancer compares favorably with those involving weekly injections. Application of this model to study the effect of dietary protein in HPOP-induced carcinogenicity showed that the number of cystic, intermediate and tubular complexes in the pancreas was significantly higher in animals fed a 20% as compared to an 8% protein diet 2 weeks prior to HPOP administration. Furthermore, the incidence of pancreatic adenocarcinomas andin situcarcinomas was only 13% in the hamsters fed the low-protein diet as compared to 46% in those fed the high-protein diet.