DNA CONTENT OF DYSPLASTIC LESIONS IN HUMAN AND RAT LIVER

人和大鼠肝脏不典型病变的 DNA 含量

• 批准号: 3172939
• 负责人: OSCAR SUDILOVSKY
• 金额: $ 14.21万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172939
• 关键词: DNA; aneuploidy; autologous transplantation; cancer risk; chemical carcinogenesis; chemical related neoplasm /cancer; densitometry; hepatectomy; hepatocellular carcinoma; histology; human tissue; liver cirrhosis; liver disorder; liver transplantation; microspectrophotometry; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer transplantation; nutrition related tag; pathogenic diet; postmortem; preneoplastic state

In preliminary experiments, it has been observed by cytospectrophotometric methods that a small number of nodules, induced in rat livers by an induction-promotion regimen, have an aneuploid modal DNA content. Since aneuploidy is associated with tumor progression, it is likely that its presence constitutes a "risk factor" for those nodules where it appears. There is no data available on nuclear DNA content in "liver cell dysplasia," a lesion in humans which is analogous to the rodent liver nodule. It is proposed to examine liver nodules induced in rats as before, using cytospectrophotometric and histochemical methods, to determine: a) if aneuploidy is associated with either partial hepatectomy, initiation, or initiation and promotion; b) the proportion of hepatomas with aneuploid pattern generated; c) the comparative effects of "stop experiments" and continuous promotion on aneuploid nodules; and d) the possible correspondence between aneuploidy and persistence or remodelling of the nodules. It is further proposed that aneuploidy is a "risk factor" for malignant transformation; this hypothesis will be tested by statistical analysis of data obtained and by intrasplenic transplantation of preneoplastic nodules. The likelihood that human liver cell dysplasia is a premalignant condition akin to some rat liver nodules will also be evaluated in autopsy cases with liver cirrhosis and/or hepatoma, by cytospectrophotometric detection of possible aneuploid modal DNA distribution. The experiments proposed may lead to: a) future exploration of possible mechanisms resulting in the aneuploid nuclear DNA content; b) less restrictive but more veritable regulations for in vivo tests of hepatocarcinogenesis; and c) improved prognostic value of liver biopsies, regarding the probability of hepatoma in human patients with liver cirrhosis.

在初步的实验中，已观察到的细胞分光光度计 方法：用免疫组织化学方法在大鼠肝脏中诱导少量结节， 诱导-促进方案，具有非整倍体模态DNA含量。 以来 非整倍体与肿瘤进展相关，很可能其 这种存在对出现这种情况的结核构成“风险因素”。 没有关于“肝细胞”中核DNA含量的数据 发育不良”，一种类似于啮齿动物肝脏的人类病变 结节。 建议如前所述检查大鼠中诱导的肝结节，使用 细胞分光光度法和组织化学方法，以确定：a）如果 非整倍体与部分肝切除术、启动或 启动和促进; B）具有非整倍体的肝癌的比例 生成的模式; c）“停止实验”和“停止实验”的比较效果 在非整倍体结节上的连续促进;和d）可能的 非整倍体和持续或重塑之间的对应关系， 结节 进一步提出，非整倍体是一个“风险因素”， 恶性转化;这一假设将通过统计学检验 分析获得的数据，并通过脾内移植 癌前结节 人类肝细胞发育不良是一种 类似于一些大鼠肝结节的癌前病变也将被 在肝硬化和/或肝癌尸检病例中进行评价， 细胞分光光度法检测可能的非整倍体模式DNA 分布 建议的实验可能导致：a）未来可能的探索 导致非整倍体核DNA含量的机制; B）较少 限制性的，但更真实的规定，在体内试验， 肝癌发生;和c）改善肝活检的预后价值， 关于人类肝细胞癌患者中肝癌的概率 肝硬化