METABOLISM AND BIOAVAILABILITY OF MEIOX FROM FRIED BEEF

拟议工作的总体目标是确定代谢 和生物利用度的诱变剂MeIQx，因为它发生在地壳的 炸牛肉。 为了表征该物质的生物利用度， 计划指定代谢活化和失活途径，以及 大分子结合，在体外和体内。 此外，吸收， MeIQx及其代谢产物的排泄和组织处置将 测定 拟议的工作是一项合作努力， 研究合成化学和新陈代谢。 的具体目标 主要的合成工作有：1）MeIQx和[C14] MeIQx的合成，2） [14 C] N-OH-MeIQx合成，3）MeIQx-核苷酸加合物的制备， （4）合成MeIQx可能的解毒产物。 的 代谢研究的目的是：1）鉴定活化的 和MeIQx的失活代谢物，2）吸收， MeIQx的体内分布、排泄和大分子结合 加入了牛肉脆皮 MeIQx是最常见的杂环诱变剂和致癌物 在炸过的肉里。 这些物质的一个独特特征是它们 定位在炸肉的外壳中。 这一特点可能会影响 化合物在胃肠中吸收的程度 因此，这些物质的毒性作用。 一个 了解肉类对生物化学特性的影响， 需要诱变剂来推断动物结果， 评估人类风险。

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.