MECHANISMS FOR MAMMARY CARCINOGENICITY OF FOOD DERIVED HETEROCYCLIC AMINES

致癌物质苯丙氨酸(2-Amino-1-methyl-6-phenylimidazo[4，5-b]pyridine) 在熟肉中，被确定为乳腺癌的致癌物 雌性Spraogue-Dawley大鼠高脂饮食。根据我们的协议， 肿瘤是由10剂量的PhIP方案诱导的，在短时间内 潜伏期(治疗后25周)。PhIP诱导的乳房 研究表明，肿瘤发病率和质量受 喂给老鼠的饮食脂肪。高脂肪饮食(23.5%玉米油) 导致乳房的发病率和重量增加两到三倍 与低脂饮食(5%玉米油)相比，更容易罹患腺癌。来阐明可能的 PhIP诱发乳腺癌的机制及饮食的影响 脂肪、肿瘤正在通过单链进行基因改变检查 构象多态性-聚合酶链式反应(SSCP-PCR) 方法：差异显示、基因克隆、DNA测序。 肿瘤正在被培养以建立细胞遗传学的细胞系 分析。到目前为止，已经建立了两个上皮细胞系，并且 G显带和染色体涂色正在进行中。到目前为止， 大约50%的肿瘤被发现携带突变密码子 H-ras基因分别为12和13。膳食脂肪似乎并不显著 改变携带H-ras突变的肿瘤的百分比。通过 差异显示，有几个基因已经被证明是 在肿瘤和正常乳腺之间的差异表达，以及 基因克隆目前正在进行中。P53突变似乎并不是 PhIP诱导的大鼠乳腺肿瘤形成的一个特征，但研究 正在检测乳腺肿瘤中P53的表达，并 正常的乳腺。RT-聚合酶链式反应显示neu基因高表达。 在大约75%的肿瘤中。Neu的过度表达不是由于 Southern印迹分析显示基因扩增。到目前为止，没有 在PhIP诱导的大鼠中发现了neu癌基因的突变 乳腺肿瘤。

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen in cooked meat, was determined to be a mammary gland carcinogen in female Sprague-Dawley rats on a high fat diet. With our protocol, tumors are induced following a 10-dose regimen of PhIP after a short latency period (25 weeks after treatment). The PhIP-induced mammary tumor incidence and mass was shown to be affected by the level of dietary fat given to the rats. A high-fat diet (23.5% corn oil) resulted in a two- to threefold higher incidence and weight of mammary gland cancer than a low fat diet (5% corn oil). To elucidate possible mechanisms of PhIP-induced mammary gland cancer and effect of dietary fat, tumors are being examined for genetic alterations by single strand conformation polymorphisms-polymerase chain reaction (SSCP-PCR) methods, differential display and gene cloning, and DNA sequencing. Tumors are being cultured to establish cell lines for cytogenetic analysis. Two epithelial cell lines have been established so far, and G-banding and chromosomal painting are underway. To date, approximately 50% of tumors have been found to carry mutations codons 12 and 13 of H-ras gene. Dietary fat does not appear to significantly alter the percentage of tumors carrying the H-ras mutations. By differential display, several genes have been shown to be differentially expressed between tumor and normal mammary gland, and gene cloning is currently underway. P53 mutations do not appear to be a feature in PhIP-induced rat mammary gland tumorigenesis, but studies are ongoing to examine p53 expression in mammary gland tumors and normal mammary gland. RT-PCR demonstrated a higher expression of neu in approximately 75% of tumors. The overexpression of neu is not due gene amplification, as shown by southern blot analysis. To date, no mutations in the neu oncogene have been found in PhIP-induced rat mammary tumors.