ENVIRONMENTAL COCARCINOGENS--FLUORANTHENE AND PYRENE

环境致癌物——荧蒽和芘

基本信息

批准号：
3447639
负责人：
Joseph E Rice
金额：
$ 5.87万
依托单位：
INSTITUTE FOR CANCER PREVENTION
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：
1985-04-01 至 1988-03-31
项目状态：
已结题

项目摘要

Fluoranthene and pyrene and found throughout the human environment. These polycyclic aromatic hydrocarbons (PAH) are formed together with benzo[a]pyrene (BaP) primarily by incomplete combustion of organic matter. Several studies have demonstrated that fluoranthene and pyrene exert a cocarcinogenic effect on BaP although neither compound is active as a tumor promoter. It has been demonstrated in our laboratory that fluoranthene and pyrene, when applied together with BaP in vivo in mouse skin, lead to increased levels of BaP-DNA adduct formation as compared to BaP alone. The objective of this proposal is to determine the molecular basis for this observation. The effect of fluoranthene and pyrene on the in vivo metabolism of BaP in mouse skin will be determined. These studies will address the question of whether the cocarcinogens induce metabolic activation of BaP in mouse skin or compete for detoxification pathways. The metabolism of fluoranthene and pyrene in vivo in mouse skin will also be studied. Major metabolites will be evaluated for their effect on the in vivo formation of BaP-DNA adducts in mouse skin. The effects of these same metabolites on the in vivo metabolism of BaP in mouse skin will also be determined. The possibility that electrophilic metabolites of fluoranthene and pyrene can bind to mouse skin DNA, RNA, and proteins will be evaluated. Metabolites of fluoranthene and pyrene which lead to increased BaP-DNA adduct formation and electrophilic metabolites found to bind to cellular macromolecules will be assayed for cocarcinogenicity on mouse skin.

荧蒽和芘遍布人类环境中。这些多环芳烃 (PAH) 与以下物质一起形成苯并[a]芘（BaP）主要通过有机物的不完全燃烧产生。多项研究表明荧蒽和芘具有尽管这两种化合物都没有肿瘤活性，但对 BaP 有致癌作用发起人。我们的实验室已证明荧蒽和当芘与 BaP 一起应用于小鼠皮肤体内时，会导致与单独的 BaP 相比，BaP-DNA 加合物形成水平增加。这该提案的目的是确定这一点的分子基础观察。荧蒽和芘对 BaP 体内代谢的影响鼠标皮肤将被确定。这些研究将解决以下问题协致癌物是否会诱导小鼠皮肤中 BaP 的代谢激活或争夺解毒途径。荧蒽的代谢还将研究小鼠皮肤体内的芘。主要代谢物将评估其对 BaP-DNA 加合物体内形成的影响在老鼠的皮肤里。这些相同的代谢物对体内的影响小鼠皮肤中 BaP 的代谢也将被测定。可能性荧蒽和芘的亲电代谢物可以与小鼠结合将评估皮肤 DNA、RNA 和蛋白质。荧蒽的代谢物和芘，导致 BaP-DNA 加合物形成增加，发现与细胞大分子结合的亲电子代谢物将测定小鼠皮肤的致癌性。