ONCOGENES AND TRANSPLACENTAL CARCINOGENESIS

胎儿组织对化学和物理的影响更敏感 比成人组织更容易致癌 这表明胚胎和 孕妇的胎儿患癌症的风险更大， 环境暴露比成年人更严重。 因此 重要的是要进一步了解有助于 调节胎儿机体对环境毒物的反应， 确定个体胎儿的遗传背景如何调节 对环境致癌物的反应。这项研究的目标将 是为了确定控制发病机制的分子机制， 小鼠肺肿瘤对多环芳烃的敏感性不同 烃介导的肿瘤形成。 生物检测将确定 经胎盘暴露于3-甲基胆蒽后的肿瘤产量 小鼠对CYPIA 1的诱导作用不同，这将允许 肿瘤发病率与代谢表型相关， 胎儿 通过分析癌基因RNA表达水平和检测 通过高灵敏度聚合酶选择致癌基因位点进行突变 链反应技术，特定模式的癌基因过度/不足- 可以在肿瘤模型中建立表达和/或突变。 它 将是特别有趣的，以确定是否差异， 胎儿对3-甲基胆蒽的代谢能力导致 突变谱在分子水平上的差异，可能是 同一基因的不同片段发生损伤的结果，或 发生在不同基因位点的突变。 该项目提供了一个 这是一个独特的机会，可以证明双方所发挥的重要作用， 遗传和环境因素在决定易感性的 个体对诱发肺肿瘤的作用。 数据将显示 个体的基因构成会影响癌症的易感性 是由于在子宫内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.