TRANSPLACENTAL CARCINOGENESIS OF HETEROCYCLIC AMINES

在传统烹调肉类的过程中，高度致癌 生成杂环胺。这些化合物需要新陈代谢 通过细胞色素P-4501a家族酶的激活来发挥 它们的致癌作用。经胎盘暴露于这些杂环 研究表明，胺可能在肿瘤的发生中发挥重要作用 通过这个实验室和其他实验室已经证明了 使其特别容易发生肿瘤的胎儿，通过 环境致癌物质。这项研究的目标将是确定 典型的饮食杂环胺的胎盘致癌作用， 2-氨基-3-甲基咪唑[4，5-f]喹啉(IQ)。这项研究将评估 靶器官特异性和Cyp1a1在转化中的潜在作用 宫内接触铅对致癌代谢物智商的影响 致癌物质。诱导肿瘤的发病机制也将是 在分子生物学水平上进行检测。生物化验将确定 小鼠经胎盘暴露后各器官的肿瘤成瘤率 胎儿对智商的影响。智商提高Cyp1a1水平的能力将是 通过生化和Northern印迹分析进行鉴定。组织产生于 生物化验将被包埋在石蜡中，并用于确定类型 在选定的致癌基因座上由智商介导的遗传损伤 人类癌症，特别是Ki-ras和p53基因。通过对这些问题的分析 用高灵敏聚合酶链法检测致癌基因突变 反应技术，癌基因突变的特定模式可能是 建立了肿瘤模型。随之而来的诱发肿瘤 经胎盘期的智商治疗将显示化学物质如何 可能会导致癌症的发生，原因是母亲的饮食中含有 在子宫内暴露于这些饮食致癌物质。

During the preparation of meat by conventional cooking, highly carcinogenic heterocyclic amines are generated. These compounds require metabolic activation by the cytochrome P-4501A family of enzymes in order to exert their carcinogenic effects. Transplacental exposure to these heterocyclic amines may play an important role int he initiation of tumors, as studies by this and other laboratories have demonstrated the unique qualities of the fetus that render it particularly susceptible to tumor initiation by environmental carcinogens. The goal of this research will be to determine the transplacental carcinogenicity of a typical dietary heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). This study will assess the target organ specificity and the potential role of Cyp1a1 in the conversion of iQ to proximate carcinogenic metabolites following in utero exposure to the carcinogen. The pathogenesis of the induced tumors will also be examined at the molecular biological level. Bioassays will determine the tumor yield in various organs following transplacental exposure of mouse fetuses to IQ. The ability of IQ to increase the levels of Cyp1a1 will be assessed by biochemical and northern blot assays. Tissue generated from the bioassay will be embedded in paraffin and used to determine the types of genetic damage mediated by IQ at selected oncogenic loci implicated in human cancer, in particular the ki-ras and p53 genes. By analysis of these oncogenic loci for mutations by the highly sensitive polymerase chain reaction technique, particular patterns of oncogene mutation can be established in the tumor models. The induction of tumors following treatment during the transplacental period with IQ will show how chemicals contained in the mother's diet can lead to cancer initiation as a result of the in utero exposure to these dietary carcinogens.