MECHANISM OF CARCINOGENESIS BY PEROXISOME PROLIFERATORS

我近期和长期的职业目标是积极参与 在致癌方面的研究。我计划通过以下方式来研究这些机制 哪些过氧化物酶增殖物可诱发肝细胞癌。我是 检验过氧化物酶增殖物诱导肝细胞的假说 癌症通过1)引起氧化DNA损伤，2)增加长期的 细胞增殖，或3)二十烷类化合物代谢改变。我们会比较一下 环丙贝特与不寻常的过氧化物酶体增殖物全氟癸酸 酸，与大多数其他过氧化物酶增殖剂不同，它抑制 过氧化物体-β氧化，增加谷胱甘肽浓度，并 没有促进活动，为他们的能力生产以上 改变。将产生肝脏特异表达的转基因小鼠 过氧化物体增殖物诱导的基因，从而使基因改变 产生由过氧化物酶体增殖物诱导的生化变化 已确认身份。

My immediate and long-term career objectives are to actively engage in research in the area of carcinogenesis. I plan to study the mechanisms by which peroxisome proliferators induce hepatocellular carcinomas. I am testing the hypotheses that peroxisome proliferators induce hepatocellular carcinomas by 1) inducing oxidative DNA damage, 2) increasing long-term cell proliferation, or 3) altering eicosanoid metabolism. We will compare ciprofibrate with the unusual peroxisome proliferator perfluorodecanoic acid, which, unlike most other peroxisome proliferators, inhibits peroxisomal beta-oxidation, increases glutathione concentrations, and does not have promoting activity, for their abilities to produce the above changes. Transgenic mice will be produced with liver specific expression of peroxisome proliferator-induced genes so that the genetic change that produces biochemical changes induced by peroxisome proliferators can be identified.