METABOLISM AND BIOAVAILABILITY OF MEIOX FROM FRIED BEEF

油炸牛肉中 MEIOX 的代谢和生物利用度

基本信息

批准号：
3181294
负责人：
HENRY RAPOPORT
金额：
$ 10.83万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 1989-08-31
项目状态：
已结题

项目摘要

The overall objectives of the proposed work are to determine the metabolism and bioavailability of the mutagen MeIQx, as it occurs in the crust of fried beef. In order to characterize bioavailability of this substance we plan to specify routes of metabolic activation and deactivation, and macromolecular binding, in vitro and in vivo. In addition, absorption, excretion and tissue disposition of MeIQx and its metabolites will be determined. The proposed work is a collaborative effort which combines studies in synthetic chemistry and in metabolism. The specific objectives of the synthetic work are: 1) synthesis of MeIQx and [C14] MeIQx, 2) synthesis of [14C] N-OH-MeIQx, 3) preparation of a MeIQx-nucleotide adduct, and 4) synthesis of likely detoxification products of MeIQx. The objectives of the metabolism studies are: 1) identification of activated and deactivated metabolites of MeIQx, in vitro, and 2) absorption, distribution, excretion, and macromolecular binding in vivo, of MeIQx incorporated in beef crust. MeIQx is the most prevelent of the heterocyclic mutagens and carcinogens which occur in fried meat. A unique feature of these substances is their localization in the crust of fried meat. This characteristic may affect the extent to which the compounds are absorbed in the gastronintestinal tract and consequently the toxic effects of the substances. An understanding of the effects of meat on the biochemical characteristics of the mutagen is rquired for efforts to extrapolate results with animals to estimates of human risk.

拟议工作的总体目标是确定新陈代谢以及诱变剂 MeIQx 的生物利用度，因为它存在于地壳中炒牛肉。为了表征该物质的生物利用度，我们计划指定代谢激活和失活的途径，以及体外和体内大分子结合。此外，吸收、 MeIQx 及其代谢物的排泄和组织处置将决定。拟议的工作是一项协作努力，结合了研究合成化学和新陈代谢。具体目标合成工作包括：1) MeIQx 和 [C14] MeIQx 的合成，2) [14C]N-OH-MeIQx的合成，3)MeIQx-核苷酸加合物的制备， 4) MeIQx可能的解毒产物的合成。这代谢研究的目标是： 1) 鉴定活化的和 MeIQx 的灭活代谢物，体外，和 2) 吸收， MeIQx 的体内分布、排泄和大分子结合并入牛肉皮中。 MeIQx 是最常见的杂环诱变剂和致癌物出现在炸肉中。这些物质的独特之处在于它们定位于炸肉的外皮中。这个特性可能会影响化合物在胃肠道中被吸收的程度道，从而影响物质的毒性作用。一个了解肉类对生化特性的影响需要使用诱变剂来推断动物的结果人类风险的估计。