BIOAVAILABILITY AND ACTIVATION OF DIETARY CARCINOGENS

膳食致癌物的生物利用度和活性

• 批准号: 2154654
• 负责人: Margaret Olive James
• 金额: $ 19.9万
• 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/2154654
• 关键词: DNA; Malacostraca; acetylation; alternatives to animals in research; 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.

海洋十足甲壳类动物的自然发生率很低 肿瘤，即使已经表明螃蟹和龙虾含有 相对较高浓度的procarcinogen，例如多环子 从污染的水上收获时，芳烃。 原因 将研究这种对肿瘤的明显抗药性 龙虾作为型号。 要调查的过程是参与 癌变的启动，即促促促骨脂的生物转化至 最终致癌物，以及最终致癌物与DNA和其他的结合 细胞大分子。 相关调查将确定 转移procarcinogen或其反应性代谢物的潜力 （近端致癌物）从甲壳酸酯到鱼。 体外和体内研究中的棘小龙虾研究将研究因素 调节procarcinogen生物活化，解毒和排泄 作为最终致癌物与DNA和其他大分子的结合。 所使用的技术将主要建立生化和 生理方法，将采用放射性标记的procarcinogens 确保足够的灵敏度。 这些研究的结果在三个领域将很重要：首先 了解对化学抗性的生物学基础 刺龙虾和其他甲壳类动物表现出的致癌作用； 其次，在预测食用procarcinogen的动物时是否暴露 甲壳类会吸收由甲壳类动物和 因此，发生肿瘤的风险增加；第三，在 提供有关影响异种生物的因素的基本信息 无脊椎动物中的生物转化。