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: 3172938
• 负责人: OSCAR SUDILOVSKY
• 金额: $ 15.31万
• 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 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172938
• 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.

在初步实验中，用细胞分光光度法观察到