CARCINOGENIC INTERACTIONS OF RADIATION AND CHEMICALS

这个项目的长期目标是确定细胞和 辐射后的分子变化导致乳腺肿瘤的发生。 使用体内/体外模型，该实验室之前的研究已经 在小鼠乳腺上皮细胞中发现了表型变化 先于Balb/c雌性小鼠乳腺肿瘤的形成。这些 研究也证实了细胞的癌前性质。 表现出这些表型变化的。在上一次授权期内，这些 模型被用来研究特定改变的牵涉 癌基因和抑癌基因中的这些表型变化。 这些数据有力地表明，肿瘤抑制因子的变化 P53基因作为早期事件参与肿瘤的发生发展 辐射暴露后的发育。对这笔下一笔拨款的研究 Period就是为了检验这一假设而设计的。 具体地说，本研究的目的是：1)确定 P53基因突变是癌前病变过程中的早期事件 照射后发育。研究将检查突变是否 在P53中一直与诱导癌前细胞相关 这些突变是否在辐射后早期被检测到 以及是否在体内观察到这种突变在导管中 发育不良。2)确定P53在肿瘤中的功能作用 小鼠乳腺细胞的研究进展。这些研究将检验影响 P53基因突变对细胞表型和细胞功能的影响。3)确定 早期辐射是否先于P53的改变 基因改变。这些研究将检测其他早期基因 照射后乳腺上皮细胞的改变。

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.