STUDIES ON THE MAMMARY CARCINOGENICITY OF HETEROCYCLIC ARYLAMINES IN COOKED MEAT

到目前为止，已有三种杂环芳胺(HAa)被证明是乳腺。 啮齿动物模型中的致癌物：2-氨基-3-甲基咪唑[4，5-f]喹啉 (IQ)，2-amino-3，8-dimethylimidazo[4，5-f]quinoxaline(MeIQx)和2-氨基-1- 甲基-6-苯基咪唑并[4，5-b]吡啶(PhIP)。我们目前正在检查 HAA加合物在乳腺上皮中的DNA加合物及其分布 放射性标记的HAAs对乳腺组织的影响，以及HAAs和HAAs的排泄 将它们的代谢产物转化为母乳。哺乳F344大鼠的研究 表明智商、MeIQx和PhIP分布在乳腺。 DNA内收发生在乳腺中，内收水平为 PhIP最高，其次是IQ，然后是MeIQx。这三种化合物都是 排泄到母乳中。哺乳5天的幼崽表现出高水平的 胃、血、肾中来自PhIP、IQ或MeIQx的放射性 还有肝脏。幼鼠尿液对艾姆斯沙门氏菌的致突变性 化验。对幼崽的DNA加合物分析正在被检测为一种手段 评估这一暴露途径的致癌后果 刚出生的。此外，对雌性Spraogue-Dawley大鼠的研究正在进行中 为了检验和比较PhIP和IQ对乳腺肿瘤的诱导作用， 及其活性代谢产物N-羟基-PhIP和N-羟基-IQ， 分别进行了分析。在未来的研究中，预计肿瘤的产生 将检查这些化学处理产生的突变和/或 关键基因如erb-B2、p53、c-myc和c-HA-ras的扩增。

To date three heterocyclic arylamines (HAAs) have been shown to be mammary carcinogens in rodent models: 2-amino-3-methylimidazo[4,5-f]quinoline (IQ),2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). We are currently examining the DNA adduction of HAA adducts in mammary epithelium, the distribution of radiolabeled HAAs to mammary tissue, and the excretion of HAAs and their metabolites into breast milk. Studies in lactating F344 rats indicate that IQ, MeIQx, and PhIP are distributed to the mammary gland. DNA adduction occurs in mammary gland with the level of adduction being highest for PhIP followed by IQ, and then MeIQx. All three compounds are excreted into breast milk. Suckling 5-day old pups show high levels of radioactivity derived from PhIP, IQ, or MeIQx in stomach, blood, kidney, and liver. Urine of pups is mutagenic in the Ames Salmonella mutagenicity assay. DNA adduct analysis of pups is being examined as a means of assessing the carcinogenic consequence of this route of exposure to the newborn. In addition, studies are underway in female Sprague-Dawley rats to examine and compare the induction of mammary tumors with PhIP and IQ, and their reactive metabolites, N-hydroxy-PhIP, and N-hydroxy-IQ, respectively. In future studies it is anticipated that tumors arising from these chemical treatments will be examined for mutations and/or amplifications in critical genes such as erb-B2, p53, c-myc, and c-HA-ras.