DETERMINANTS OF DIETARY RISK OF HETEROCYCLIC AMINE

高蛋白食品的热加工和热解及其标准 美国人的烹饪习惯，如烤肉、油炸和烧烤 诱导形成强致突变性和致癌性杂环 胺。这些相同的化合物在多个器官部位产生了肿瘤 无论是老鼠还是大鼠。非人灵长类动物喂食其中一种杂环胺 在很短的潜伏期后患上了肝癌。此外， 流行病学研究表明，肉类消费与 人类的癌症。由于这些发现，重要的是要确定 这些诱变剂/致癌物是否会导致人类癌症的发生。 这项提议将试图通过：1)确定和量化 从饮食中摄入这些杂环胺；2)探索实用性 通过防止诱变剂形成来减少暴露的方法；3) 通过DNA分析了解这些化合物的慢性毒理作用 长期使用后的结合、细胞遗传学损伤和突变效应 喂食啮齿动物；4)研究个体人类的重要性 经评估中国仓鼠卵巢细胞的修复和代谢差异 DNA修复和代谢激活的遗传差异；5) 描述重要的代谢途径以达到理解的目的 这些物质诱导的组织特异性致癌的本质 啮齿动物和非人类灵长类动物中的杂环胺.6)了解 与低剂量辐射相关的生物剂量学 摄取这些有效的诱变剂；7)将由此产生的数据 从文献到癌症风险评估的项目和数据。在 本研究的结论，细胞遗传学损伤的基本机制， 这些化合物引起的新陈代谢和DNA加合将会更多 完全理解。此外，基于暴露的风险评估， 剂量学和药代动力学将得到发展。

Heat processing and pyrolysis of protein-rich foods along with standard American cooking practices such as broiling, frying and barbecuing of meats induce the formation of potent mutagenic and carcinogenic heterocyclic amines. These same compounds produced tumors at multiple organ sites in both mice and rats. Nonhuman primates fed one of these heterocyclic amines have developed hepatocarcinomas after a very short latency. Furthermore, epidemiology studies suggest a good correlation of meat consumption with cancer in humans. Because of these findings, it is important to determine whether these mutagens/carcinogens contribute to human cancer incidence. This proposal will attempt to do so by: 1) Identifying and quantifying dietary exposure to these heterocyclic amines; 2) Exploring practical methods of reducing exposure by preventing mutagen formation; 3) Understanding the chronic toxicology of these compounds by analysis of DNA binding, cytogenetic damage and mutational effects following long-term feeding of rodents; 4) Studying the importance of individual human differences in repair and metabolism by assessment in CHO cells having genetic differences in DNA repair and metabolic activation; 5) Characterizing important metabolic pathways with the goal of understanding the nature of the tissue-specific carcinogenesis induced by these heterocyclic amines in rodents and in nonhuman primates; 6) Understanding the biological dosimetry related to the low-dose exposures from the ingestion of these potent mutagens; 7) Subjecting data generated from this project and data from the literature to cancer-risk assessment. At the conclusion of this study, basic mechanisms of cytogenetic damage, metabolism and DNA adduction caused by these compounds will be more thoroughly understood. In addition, a risk assessment based on exposure, dosimetry, and pharmacokinetics will be developed.