BACTERIA-DNA DAMAGE IN STOMACH AND BLADDER CANCERS

胃癌和膀胱癌中的细菌 DNA 损伤

• 批准号: 3191317
• 负责人: HELMUT BARTSCH
• 金额: $ 13.72万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3191317
• 关键词: DNA; adduct; alkylation; bacterial disease; bacteriuria; biopsy; bladder neoplasm; cancer risk; chemical carcinogenesis; deoxyguanosine; disease /disorder model; gastric juice; gastritis; high performance liquid chromatography; histopathology; human subject; laboratory rat; mass spectrometry; molecular oncology; neoplasm /cancer diagnosis; nitrate reductases; nitrosamines; oxidation; preneoplastic state; stomach neoplasms

The objective of the proposed work is to investigate the role of bacterial colonization/infection in the etiology of gastric and urinary bladder cancer. Studies in human will explore the relationship of bacterial colonization of the stomach and severity of precancerous lesions with the concentration of carcinogens and their precursors in gastric juice as well as with resultant DNA damage in stomach tissue. Total N-nitroso compounds in human gastric juice will be determined by thermal energy analysis and genotoxins, assayed using the SOS chromotest, will be isolated and identified. Studies in vitro and in vivo in rodents with experimentally induced bacterial colonization/infection of the stomach and bladder will explore the mechanism by which bacteria and inflammatory changes produce alkylation and oxidation of Dna. Alkylated DNA bases in tissues will be determined by immunostaining and immunoassays and levels of 8-hydroxydeoxyguanosine, as a measure of oxidative DNA damage, will be detected by HPLC with electrochemical detection. Unknown carcinogen spectrometry. Bacterial enzymes responsible for nitrosation of amine/amides will be characterized. This approach should lead to a better understand of molecular mechanisms by which bacterial colonization/infection is involved in human carcinogenesis. Once markers for DNA damage that are associate with microbial colonization/infection in the stomach and urinary bladder have been identified, they could be exploited in subsequent epidemiological and intervention studies.

拟议工作的目的是调查 胃和胃的病因中的细菌定植/感染 泌尿膀胱癌。 人类的研究将探索 胃的细菌定植与严重程度的关系 癌性病变的浓度和致癌物的浓度 它们在胃果汁中以及由此产生的DNA中的前体 胃组织损伤。 人类的总N-硝基化合物 胃汁将通过热能分析和 使用SOS Chromotest测定的基因毒素将被分离出来，并 确定。 在体外和体内研究啮齿动物 实验诱导的细菌定植/感染 胃和膀胱将探索细菌的机制 炎症变化会产生DNA的烷基化和氧化。 组织中的烷基化DNA碱将由免疫染色确定 以及8-羟基氧鸟苷的免疫测定和水平，作为一个 HPLC将检测到氧化DNA损伤的度量 电化学检测。 未知的致癌物光谱法。 负责胺/酰胺硝化的细菌酶将 被描述。 这种方法应该可以更好地理解分子 涉及细菌定植/感染的机制 在人类致癌作用中。 一旦标记DNA损伤 与胃中的微生物定植/感染相关 已经确定了膀胱，可以利用它们 随后的流行病学和干预研究。