CARCINOGENIC INTERACTIONS OF RADIATION AND CHEMICALS

这项工作的长期目标是确定 辐射后细胞的连续变化， 乳腺肿瘤形成。 使用细胞的实验 解离（CD）和上皮病灶（EF）测定 项目期间提供了有关细胞变化的信息 基于体内和体外生长参数。 细胞系 也被用于研究肿瘤 进展 拟议的实验旨在采取 利用这些独特的机会， 模型系统，以扩展这些研究， 染色体改变、癌基因和生长因子 乳腺肿瘤发展。 细胞遗传学和分子 生物技术将被用于更全面地描述肿瘤的特征， 和观察到的乳腺癌前病变的细胞表型改变， 肿瘤发展 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 测定以：（1）确定是否特异性染色体 改变与小鼠乳腺肿瘤相关;（2） 确定特定的染色体改变是否 与观察到的表型变化相关 肿瘤发生;（3）确定特定的癌基因是否 与乳腺肿瘤相关;（4）确定是否特异性 癌基因与特定的改变的生长表型有关 在肿瘤进展期间;和（5）检查生物化学 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.