ONCOGENES AND TRANSPLACENTAL CARCINOGENESIS

胎儿组织对化学和物理的影响更敏感 致癌物比成人组织的致癌物更多。这表明胚胎和 孕妇的胎儿患癌症的风险更大 比成年人口暴露在环境中的风险更大。它是这样的 重要的是进一步了解帮助(S)的机制 调节胎儿有机体对环境毒物的反应，并 确定个体胎儿的遗传背景如何调节 它对环境致癌物质的反应。这项研究的目标将是 目的是为了确定控制慢性粒细胞白血病发病的分子机制 对多环类药物敏感性不同的小鼠肺癌 碳氢化合物介导的肿瘤形成。生物化验将确定肺部 经胎盘暴露3-甲基胆蒽对小鼠肿瘤的影响 小鼠对CYPIA1的诱导性不同，这将允许 肿瘤发病率与人的代谢表型相关 胎儿。通过对癌基因RNA表达水平的分析和对 用高灵敏聚合酶筛选突变致癌基因 链式反应技术，癌基因上/下的特殊模式- 可以在肿瘤模型中建立表达和/或突变。它 将特别有趣地确定是否存在差异 胎儿对3-甲基胆蒽的代谢能力导致 分子水平上突变谱的差异，可能是 同一基因的不同片段发生损伤的结果 发生在不同遗传位点的突变。该项目提供了一种 展示双方所发挥的重要作用的独特机会 遗传和环境因素在决定血吸虫病易感性中的作用 个体以诱发肺部肿瘤为主。这些数据将显示出 个体的基因构成会影响对癌症的易感性 由于在子宫早期暴露于环境化学物质。

Fetal tissues are more sensitive to the effects of chemical and physical carcinogens than are adult tissues. This suggests that the embryos and fetuses of pregnant women are at a greater risk of developing cancers from environmental exposures than is the adult population. It is thus important to gain further understanding of the mechanism(s) that help modulate the fetal organism's response to environmental toxicants, and to determine how the genetic background of the individual fetus can modulate its response to environmental carcinogens. The goal of this research will be to determine the molecular mechanisms governing the pathogenesis of lung tumors in mice differing in their susceptibility to polycyclic hydrocarbon-mediated tumor formation. Bioassays will determine the lung tumor yield following transplacental exposure to 3-methylcholanthrene in mice differing in their inducibility for CYPIA1, which will allow the tumor incidence to be correlated with the metabolic phenotype of the fetus. By analysis of oncogene RNA expression levels and examination of selected oncogenic loci for mutations by the highly sensitive polymerase chain reaction technique, particular patterns of oncogene over/under- expression and/or mutation can be established in the tumor models. It will be particularly interesting to determine whether differences in the metabolic capacity of the fetus toward 3-methylcholanthrene result in differences in the mutational spectrum at the molecular level, possibly as a result of damage occurring to different segments of the same gene or mutations occurring at different genetic loci . This project offers an unique opportunity to demonstrate the important role played by both genetic and environmental factors in determining the susceptibility of the individual to the induction of lung tumors. The data will show how the genetic make-up of the individual can influence susceptibility to cancer as a result of early in utero exposure to environmental chemicals.