Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis in Sprague-Dawley rats by orotic acid.
Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis in Sprague-Dawley rats by orotic acid.
复制标题
乳清酸增强 Sprague-Dawley 大鼠中 N-亚硝基（2-羟丙基）（2-氧代丙基）胺诱导的肿瘤发生。
DOI：
10.1093/carcin/12.2.181
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发表时间：
1991
期刊：
影响因子：
4.7
通讯作者：
Oyasu,R
中科院分区：
文献类型：
--
作者：
Kokkinakis,DM;Scarpelli,DG;Oyasu,R
研究了冬虫夏草酸(OA)对大鼠致癌性过氧化氢酶(ofN-nitroso(2-hydroxypropyl)(2-oxopropyl)amine)的影响。将一组5周龄的雄性SD大鼠置于合成的20%蛋白质饲料中，其中含有1%的OA。第二组受试者的饮食结构相似，不含维生素A。大约2周后，两组动物体重均达到100g，经2002年阿尔茨海默特渗透泵植入S.C.连续14天给予400 mg/kg的HPOP。在HPOP治疗开始后，喂食OA饮食的大鼠在这种饮食下持续13周，然后再按常规饮食喂养12周，然后处死它们。在没有OA的情况下，HPOP处理的大鼠发生肾脏和肺部腺瘤的发生率分别为5%和33%，而胰腺和肝脏未受影响。另一方面，饲喂OA饲料和HPOP治疗的大鼠发生肾间充质瘤和肺腺瘤的发生率分别为70%和65%。此外，HPOP在饲喂OA饮食的动物的胰腺中诱导了囊性病变。HPOP的致瘤效果的增强至少部分归因于OA治疗对致癌物诱导的DNA烷基化在不同组织中重现的速度的影响。饲喂油酸饲料的大鼠肾脏、肺和胰腺中N7-甲基鸟嘌呤的积累量分别是常规饲料动物各器官的1.6、1.9和2.4倍。类似地，喂食OA饲料的大鼠肾脏、肺和胰腺中的突变前O6-甲基鸟嘌呤(O6-Meg)浓度分别是喂食常规饲料的大鼠各自器官的3.0、3.1和2倍。给HPOP处理的大鼠喂食OA饮食既不影响肝脏对这种致癌物的抵抗力，也不影响组织DNA中O6-Meg的积累水平。
The effect of orotic acid (OA) on the carcinogenicity ofN-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) in rats was evaluated. A group of 5 week old Sprague-Dawley male rats were placed on a synthetIc 20% protein diet containing 1% OA. A second group was placed on a regular, OA free diet of similar composition. Approximately 2 weeks later, animals from both groups grown to 100 g were treated with 400 mg/kg HPOP delivered continuously for 14 days via 2002 Alzet osmotic pumps implanted s.c. Rats fed the OA diet were kept under this diet for 13 weeks following initiation of HPOP treatment and subsequently were placed on the regular diet for another 12 weeks, at which time they were killed. In the absence of OA, HPOP-treated rats developed adenomas in the kidney and lungs at incidences of 5 and 33% respectively, while pancreas and liver were unaffected. On the other hand, rats fed the OA diet and treated with HPOP developed renal mesenchymal tumors and pulmonary adenomas at incidences of 70 and 65% respectively. In addition, HPOP induced cystic lesions in the pancreas of animals fed the OA diet. The enhancement of the tumorigenic effectiveness of HPOP was at least partly ascribed to the effect of OA treatment on the rate by which carcinogen-induced alkylation of DNA was reyaired in various tissues. Accumulation ofN7-methylguanine in kidney, lung and pancreas of rats fed the OA diet was 1.6, 1.9 and 2.4 times higher than in respective organs of animals fed the regular diet. Similarly, concentrations of the premutagenicO6-methylguanine (O6-MeG) were 3.0, 3.1 and 2 times greater in the kidney, lung and pancreas of rats fed the OA diet than in the respective organs of those fed the regular diet. Feeding an OA diet to HPOP-treated rats did not have an effect on either the resistance of the liver to this carcinogen or on the level ofO6-MeG accumulation in the DNA of this tissue.