CARCINOGENIC INTERACTIONS OF RADIATION AND CHEMICALS

这项工作的长期目标是确定 照射后细胞的连续变化导致 乳腺肿瘤的形成。使用该细胞的实验 最近一次的离解(CD)和上皮灶(EF)分析 项目期间提供了有关蜂窝变化的信息 基于体内和体外生长参数。细胞系是 也开发了用于研究肿瘤的 进步。拟议中的实验旨在采取 利用这些独一无二的机会 模型系统，以扩展这些研究，以检查 染色体改变、癌基因和生长因子 乳腺肿瘤的发生。细胞遗传学和分子生物学 生物技术将被用来更全面地描述肿瘤的特征 以及在乳腺之前观察到的改变的细胞表型 肿瘤的发展。这些研究将使用肿瘤以及 从CD和EF获得的组织、原代细胞和细胞系 检测：(1)确定特定的染色体是否 改变与小鼠乳腺肿瘤有关；(2) 确定特定的染色体改变是否 与观察到的表型变化有关 肿瘤发生；(3)确定特定的癌基因是否 与乳腺肿瘤相关；(4)确定是否具有特异性 癌基因与特定的生长表型改变有关 在肿瘤进展过程中；和(5)检查生化 与改变的生长表型相关的改变。

The long term objective of this work is to determine the sequential cellular changes following irradiation leading to mammary tumor formation. Experiments using the cell dissociation (CD) and epithelial focus (EF) assays over the last project period have provided information on cellular changes based on in vivo and in vitro growth parameters. Cell lines were also developed which have been used to study neoplastic progression. The proposed experiments are designed to take advantage of the unique opportunities made possible with these model systems to extend these studies to examine the role of chromosome alterations, oncogenes and growth factors in mammary tumor development. Cytogenetic and molecular biologic techniques will be used to more fully characterize tumors and the altered cellular phenotypes observed to precede mammary tumor development. These studies will use tumors as well as tissues, primary cells, and cell lines obtained from the CD and EF assays to: (1) determine whether specific chromosomal alterations are associated with mouse mammary tumors; (2) determine whether specific chromosomal alterations are associated with phenotypic changes observed during tumorigenesis; (3) determine whether specific oncogenes are associated with mammary tumors; (4) determine whether specific oncogenes are associated with specific altered growth phenotypes during neoplastic progression; and (5) examine biochemical alterations associated with the altered growth phenotypes.