STUDIES ON THE MAMMARY CARCINOGENICITY OF FOOD-DERIVED HETEROCYCLIC AMINES

我们已经建立了一种雌性大鼠乳腺肿瘤模型，用这种药物治疗 杂环胺(HA)食品致癌物质2-氨基-1-甲基-6-苯基咪唑- [4，5-b]吡啶(PhIP)肿瘤正在接受组织学检查，而且 基因改变已确定。正在研究的基因 扩增/突变包括erb-B2、p53、c-myc和c-HA-ras。细胞 目前正在从肿瘤中提取线条，以供进一步分析。结果是 表明高脂饮食通过以下方式增强PhIP的乳腺致瘤性 增加了乳腺肿瘤的发病率和严重程度。脱氧核糖核酸 透明质酸加合物在乳腺上皮细胞中的加合作用 乳腺癌的诱癌作用，进行检测。加合物去除研究表明 PhIP-DNA加合物在上皮细胞中存在数周。 给药后。我们还检查了乳腺中HAS的内收。 哺乳期雌性大鼠在乳腺组织中的分布，以及 把HAS及其代谢物排入母乳中。DNA加成 发生在乳腺中，内收水平最高的是 Phip，然后是2-氨基-3-甲基咪唑[4，5-f]-喹啉(IQ)，然后 2-氨基-3，8-二甲基咪唑并[4，5-f]喹恶啉(MeIQx)。三个都是 化合物被排泄到母乳中。DNA加合物被检测到在 新生幼崽的组织。结果表明，这些物质已经排泄到 母乳可能会对新生儿产生致癌作用。

We have developed a mammary tumor model in female rats treated with the heterocyclic amine (HA) food carcinogen 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP). Tumors are being examined histologically, and genetic alterations determined. Genes under study for amplifications/mutations include erb-B2, p53, c-myc, and c-HA-ras. Cell lines are being derived from tumors for further analyses. The results show that a high fat diet enhances mammary tumorigenicity of PhIP by increasing the incidence and severity of the mammary tumors. DNA adduction of HA adducts in mammary epithelial cells, the target site for mammary cancer induction, was examined. Adduct removal studies show that PhIP-DNA adducts are present in the epithelial cells for several weeks after dosing. We also examined the adduction of HAs in the mammary gland of lactating female rats, the distribution to mammary tissue, and the excretion of HAs and their metabolites into breast milk. DNA adduction occurs in mammary gland with the level of adduction being highest for PhIP, followed by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), and then 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). All three compounds are excreted into breast milk. DNA adducts were detected in tissues of the newborn pups. The results suggest that HAs excreted into breast milk may have carcinogenic consequence to the newborn.