METABOLISM AND BIOAVAILABILITY OF MEIOX FROM FRIED BEEF

拟议工作的总体目标是确定新陈代谢 诱变剂MeIQx的生物利用度，因为它出现在 炸牛肉。为了表征这种物质的生物利用度，我们 计划指定代谢激活和去激活的途径，以及 大分子结合，体外和体内。此外，吸收， MeIQx及其代谢物的排泄和组织处置 下定决心。拟议的工作是一项合作努力，它结合了 研究合成化学和新陈代谢。具体目标 1)MeIQx和[C14]MeIQx的合成，2) [14C]N-OH-MeQx的合成，3)MeIQx-核苷酸加合物的制备， 4)可能的MeIQx解毒产物的合成。这个 代谢研究的目标是：1)确定被激活的 和灭活的MeIQx代谢物，体外，和2)吸收， MeIQx在体内的分布、排泄和大分子结合 加进牛肉皮里。 MeIQx是杂环诱变剂和致癌物中最常见的 这种物质存在于炸肉中。这些物质的一个独特特征是它们的 在油炸肉皮中的定位。这一特征可能会影响 化合物在胃肠道中被吸收的程度 因此，这些物质的毒性影响。一个 了解肉类对肉制品生化特性的影响 这种诱变剂是用动物来推断结果所必需的 对人类风险的估计。

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.