STUDIES ON THE MAMMARY CARCINOGENICITY OF HETEROCYCLIC ARYLAMINES IN COOKED MEAT

迄今为止，三种杂环芳胺（哈斯）已被证明是乳腺癌 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-氨基-3，8-二甲基咪唑并[4，5-f]喹喔啉（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加合物在乳腺上皮细胞中的DNA加合， 放射性标记的哈斯进入乳腺组织，以及哈斯和 它们的代谢产物进入母乳。 哺乳期F344大鼠研究 表明IQ、MeIQx和PhIP分布到乳腺。 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 分泌到母乳中。 哺乳期5天大的幼崽显示出高水平的 来自胃、血液、肾脏中PhIP、IQ或MeIQx的放射性， 和肝脏。 幼仔尿液在艾姆斯沙门氏菌致突变性中具有致突变性 比色法 正在研究对幼崽进行DNA加合物分析， 评估这种接触途径的致癌后果， 新生儿 此外，在雌性Sprague-Dawley大鼠中进行的研究正在进行中。 为了检查和比较PhIP和IQ对乳腺肿瘤的诱导， 及其活性代谢物N-羟基-PhIP和N-羟基-IQ， 分别 在未来的研究中，预计出现的肿瘤 将检查这些化学处理的突变和/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.