MECHANISM OF CARCINOGENESIS BY PEROXISOME PROLIFERATORS

我的近期和长期职业目标是积极参与 在致癌领域的研究。 我计划通过以下方式来研究其机制 过氧化物酶体增殖物诱导肝细胞癌。 我是 检验过氧化物酶体增殖物诱导肝细胞癌的假设 通过1）诱导氧化性DNA损伤，2）增加长期 细胞增殖，或3）改变类花生酸代谢。 我们将比较 环丙贝特与罕见的过氧化物酶体增殖剂全氟癸酸 酸，不像大多数其他过氧化物酶体增殖剂， 过氧化物酶体β-氧化，增加谷胱甘肽浓度， 没有促进活动，为他们的能力，以产生上述 变化 将产生具有肝脏特异性表达的转基因小鼠 过氧化物酶体增殖物诱导的基因， 产生由过氧化物酶体增殖物诱导的生化变化， 鉴定

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.