CARCINOGENIC INTERACTIONS OF RADIATION AND CHEMICALS

该项目的长期目标是确定细胞和 照射后的分子变化导致乳腺肿瘤的发展。 使用体内/体外模型，本实验室先前的研究 在小鼠乳腺上皮细胞中鉴定了表型改变， 在Balb/c雌性小鼠中发生乳腺肿瘤之前。 这些 研究还证实了细胞的癌前性质 表现出这些表型变化。 在过去的一段时间里，这些 模型被用来调查参与特定的改变， 癌基因和抑癌基因在这些表型改变中的作用。 这些数据有力地表明，肿瘤抑制基因的改变， p53基因作为早期事件参与了肿瘤的发生过程。 辐射暴露后的发展。 下一笔拨款的研究 这一时期旨在检验这一假设。 具体而言，本研究的目的是：1）确定是否 p53突变是肿瘤前病变时间进程中的早期事件， 辐照后的发展。 研究将检验突变是否 在p53中的表达与肿瘤前细胞一致相关， 辐射，这些突变是否在辐射后早期被检测到， 辐射，以及是否在导管中体内观察到这种突变， 发育不良 2)确定p53在肿瘤中的功能作用 小鼠乳腺细胞的进展。 这些研究将检验 改变p53对细胞表型和细胞功能的影响。 3)确定 p53的改变是否先于早期辐射诱导的 基因改变 这些研究将检查其他早期遗传 辐照乳腺上皮细胞的变化。

The long term objective to this project is to determine cell and molecular changes after irradiation leading to mammary tumor development. Using in vivo/in vitro models, previous studies in this laboratory have identified phenotypic alterations in mouse mammary epithelial cells which precede the development of mammary tumors in Balb/c female mice. These studies have also confirmed the preneoplastic nature of the cells exhibiting these phenotypic changes. Over the last grant period, these models were used to investigate the involvement of specific alterations in oncogenes and tumor suppressor genes in these phenotypic changes. These data strongly suggest that alterations in the tumor suppressor gene, p53, are involved as early events in the process of neoplastic development following radiation exposure. Research over this next grant period is designed to test this hypothesis. Specifically, the aims of this research are to: 1) Determine whether mutations in p53 are early events in the time course of preneoplastic development after irradiation. Studies will examine whether mutations in p53 are consistently associated with preneoplastic cells induced by irradiation, whether these mutations are detected early after irradiation, and whether such mutations are observed in vivo in ductal dysplasias. 2) Determine the functional role of p53 in neoplastic progression of murine mammary cells. These studies will examine effects of altered p53 on cellular phenotype and cell function. 3) Determine whether alterations in p53 are preceded by earlier radiation induced genetic alterations. These studies will examine other early genetic alterations in irradiated mammary epithelial cells.