DNA DAMAGE INDUCED BY PANCREATROPIC NITROSAMINES

胰亚硝胺引起的 DNA 损伤

• 批准号: 3184807
• 负责人: DEMETRIUS Michael KOKKINAKIS
• 金额: $ 11.52万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184807
• 关键词: DNA repair; DNA replication; binding proteins; carcinogen testing; chemical addition; chemical carcinogen; chemical carcinogenesis; chemical structure function; dietary aminoacid; dietary proteins; hamsters; kidney neoplasms; laboratory rat; liver neoplasms; lung neoplasms; molecular oncology; nitrosamines; nitroso compounds; nutrition related tag; pancreas neoplasms; radiotracer; toxin metabolism

N-Nitroso-2, 6-dimethylmorpholine (NNDM), N-Nitrosobis(2- oxopropyl)amine (BOP), N-Nitrosobis(2-hydroxypropyl)amine (BHP), and N-Nitroso(2-hydroxypropyl) (2-oxopropyl) amine (HPOP) induce tumors of the pancreas, lungs, gallbladder, kidneys and bladder in hamsters and upper respiratory tract, esophagus, liver, and kidney tumors in rats. Organotropy of these carcinogens depends on dose, sex, frequency and route of administration. Differences between species in pancreas carcinogenesis and between sexes in liver carcinogenesis are marked and useful in the elucidation of the mechanism of action of these carcinogens. It is proposed to study the relationships among metabolism, tissue injury and carcinogenesis in rats and hamsters treated mainly with HPOP, but also with NNDM and BHP. The aims of this study are: 1) Develop the methodology to characterize and quantitate DNA adducts which are formed and persist in various tissues of hamsters and rats during continuous administration of NNDM, BHP and HPOP. 2) Design regimens of continuous administration of these carcinogens which will cause a high incidence of pancreatic tumors. 3) Measure labeling of tissue and DNA of target and nontarget organs during treatment of hamsters and rats with radiolabeled nitrosamines, and also evaluate possible relations between tumor induction and persistence of various DNA adducts. 4) Evaluate the rate of repair of various adducts by measuring the decline of their concentration in DNA and tissues of animals treated either with a single dose of carcinogen or continuously for 7 days. 5) Test the capacity of rats and hamsters to metabolize xenobiotics including the carcinogenic nitrosamines following the treatment period. Also test the activity of phase I and phase II enzymes in the liver and the ability of various tissues to repair 06 MeGuanosine following the treatment with carcinogenic nitrosamines. 6) Investigate the levels of adducts and the rate of their repair in component cells of the pancreas and liver of animals undergoing treatment with HPOP or following such treatment. 7) Examine the effect of low protein diet, methionine-deficient diet and inhibitors of sulfation of HPOP on the carcinogenicity of HPOP in hamsters. Evaluate the effect of such treatment on the formation and repair of DNA adducts in various organs of the animals.

n -亚硝基- 2,6 -二甲基啉（NNDM）

项目成果

Metabolism and activation of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine by isolated hepatocytes and pancreatic cells of the Syrian hamster.

叙利亚仓鼠分离的肝细胞和胰腺细胞对胰腺致癌物 N-亚硝基双（2-氧代丙基）胺的代谢和激活。

• DOI: 10.1093/carcin/11.4.625
• 发表时间: 1990
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Mangino,MM;Scarpelli,DG;Kokkinakis,DM
• 通讯作者: Kokkinakis,DM

Alkylation of rodent tissue DNA induced by N-nitrosobis(2-hydroxypropyl)amine.

N-亚硝基双（2-羟丙基）胺诱导啮齿动物组织 DNA 的烷基化。

• DOI: 10.1093/carcin/13.5.759
• 发表时间: 1992
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Kokkinakis,DM

Differences between pancreatropic nitrosamine carcinogens and N-nitrosodimethylamine in methylating DNA in various tissues of hamsters and rats.

促胰亚硝胺致癌物和 N-亚硝基二甲胺对仓鼠和大鼠各组织 DNA 甲基化的差异。

• DOI: 10.1016/0009-2797(91)90012-v
• 发表时间: 1991
• 期刊: Chemico-biological interactions
• 影响因子: 5.1
• 作者: Kokkinakis,DM

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

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
• 发表时间: 1989
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Kokkinakis,DM;Scarpelli,DG
• 通讯作者: Scarpelli,DG

Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis in Sprague-Dawley rats by orotic acid.

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
• 发表时间: 1991
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Kokkinakis,DM;Scarpelli,DG;Oyasu,R
• 通讯作者: Oyasu,R