BIOAVAILABILITY AND ACTIVATION OF DIETARY CARCINOGENS

膳食致癌物的生物利用度和活性

• 批准号: 3254110
• 负责人: Margaret Olive James
• 金额: $ 21.72万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3254110
• 关键词: DNA; Malacostraca; acetylation; amines; benzopyrenes; biotransformation; carbopolycyclic compound; chemical addition; chemical carcinogen; cyclic amine; cytochrome P450; detoxification; environmental toxicology; glutathione transferase; glycosylation; high performance liquid chromatography; molting; monophenol monooxygenase; phenols; saltwater environment; temperature; water environment

Marine decapod crustaceans have a very low reported natural incidence of neoplasia, even though it has been shown that crabs and lobsters contain relatively high concentrations of procarcinogens such as polycyclic aromatic hydrocarbons when harvested from polluted waters. Reasons for this apparent resistance to neoplasia will be investigated, with the spiny lobster as model. Processes to be investigated are those involved in the initiation of carcinogenesis, namely biotransformation of procarcinogens to ultimate carcinogens, and binding of ultimate carcinogens to DNA and other cellular macromolecules. Related investigations will determine the potential for transfer of procarcinogens or their reactive metabolites (proximate carcinogens) from crustacea to fish. In vitro and in vivo studies in spiny lobster will investigate factors modulating procarcinogen bioactivation, detoxication and excretion as well as the binding of ultimate carcinogens to DNA and other macromolecules. The techniques used will mainly be established biochemical and physiologicaL methods and will employ radiolabelled procarcinogens to ensure adequate sensitivity. Results of these studies will be of importance in three areas: firstly, in understanding the biological basis for resistance to chemical carcinogenesis exhibited by the spiny lobster and other crustaceans; secondly, in predicting whether animals which eat procarcinogen-exposed crustacea will absorb proximate carcinogens formed by the crustacean and therefore be at increased risk for developing neoplasms; thirdly, in providing basic information about factors influencing xenobiotic biotransformation in invertebrates.

海洋十足目甲壳类动物的自然发病率非常低 肿瘤，尽管已经表明螃蟹和龙虾含有 相对较高浓度的致癌物质，例如多环 从受污染的水中收集时会产生芳香烃。 原因 将研究这种对肿瘤的明显抵抗力， 以龙虾为模型。 要调查的流程是涉及以下内容的流程： 致癌作用的启动，即致癌物生物转化为 最终致癌物，以及最终致癌物与DNA和其他物质的结合 细胞大分子。 相关调查将确定 致癌物或其反应性代谢物转移的潜力 （近似致癌物）从甲壳类动物到鱼类。 大龙虾的体外和体内研究将调查因素 调节致癌物质的生物活性、解毒和排泄 最终致癌物与 DNA 和其他大分子的结合。 所使用的技术将主要是已建立的生化和 生理学方法，并将采用放射性标记的致癌物 确保足够的灵敏度。 这些研究的结果在三个领域具有重要意义：首先， 了解耐化学性的生物学基础 大龙虾和其他甲壳类动物表现出致癌作用； 其次，在预测食用暴露于致癌物质的动物是否 甲壳类动物会吸收甲壳类动物形成的近似致癌物质， 因此患肿瘤的风险增加；第三，在 提供影响外源性因素的基本信息 无脊椎动物的生物转化。