EFFECT OF PHIP AND DIETARY FAT ON MAMMARY GLAND CELL BIOLOGY

为了更好地了解乳腺癌的发病机制， 杂环胺诱导 2-氨基-1-甲基-6-苯基咪唑并[4，5-B]吡啶（PhIP） 膳食脂肪，研究正在进行中，以评估影响的PhIP和 膳食脂肪对乳腺上皮细胞增殖的影响， 细胞凋亡和腺体发育。 女性 Sprague-Dawley大鼠给予致癌剂量方案 PhIP，并按照 项目Z 01 CP 05748 -3。 在致癌物质 给药后，检查大鼠乳腺的癌前病变 组织学改变 上皮细胞增殖和凋亡 免疫组织化学方法检测。 乳房全坐骑是 目前正在建立一个监测发展和分支的 高脂肪和低脂肪组致癌剂处理动物和对照动物的腺体 节食。 数据表明，致癌物治疗产生了一种 乳腺的时间依赖性萎缩。 凋亡率 对照组大鼠和PhIP处理组大鼠的腺体不同 高脂肪和低脂肪饮食。 扩散似乎也是 受致癌物处理的影响。 进一步的研究正在进行中， 定义与致癌物相关的分子改变， 膳食脂肪诱导的大鼠乳腺癌前病变。

To better understand the mechanisms involved in mammary gland cancer induction by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and the effect of dietary fat, studies are underway to assess the affect of PhIP and dietary fat on the mammary gland epithelial cell proliferation, apoptosis, and glandular development in an in vivo rat model. Female Sprague-Dawley rats were administered a carcinogenic dose regimen of PhIP and placed on either a high fat or low fat diet as described in project Z01CP05748-3. At various times after carcinogen administration, mammary glands from rats were examined for premalignant histological alterations. Epithelial cell proliferation and apoptosis were examined by immunohistochemical methods. Mammary whole mounts are currently being set-up to monitor the development and branching of the gland from carcinogen-treated and control animals on high and low fat diets. Data suggest that carcinogen treatment produces a time-dependent atrophy of the mammary gland. The rate of apoptosis in the glands was different between control rats and PhIP-treated animals on high and low fat diets. Proliferation also appeared to be influenced by carcinogen treatment. Further studies are underway to define the molecular alterations associated with the carcinogen plus dietary fat-induced premalignant changes in the rat mammary gland.