PEROXISOME PROLIFERATOR INDUCED TRANSCRIPTION FACTORS

描述 降血脂药物、增塑剂和其他化学物质导致肝脏 大鼠和小鼠肝细胞癌与过氧化物酶的增殖 然而，其他物种，包括叙利亚仓鼠、豚鼠和 灵长类动物对过氧化物体增殖物的反应较低。其作用机制 这些药物在某些物种中的作用机制尚不清楚，但在另一些物种中则不是。 但可能与诱导细胞增殖、抑制细胞增殖有关 细胞凋亡，或活性氧的产生。活性物质的生产 氧气可以导致细胞中基因表达的变化，包括 核因子-kB在无反应物种仓鼠中的激活。因此，它是 假设氧化应激在致癌过程中起重要作用 过氧化物酶体增殖物的活性。调查员提议检查 1)大鼠和大鼠细胞内抗氧化剂和抗氧化酶水平 仓鼠肝脏以确定是否发生差异减少，这可能解释 核因子-kB在大鼠中的激活，而不是在仓鼠中，以及2)是否有其他 活性氧诱导的转录因子也不同于 在这两个物种中都被激活了。这些研究将提供以下信息 将解决确定以下机制的长期目标： 过氧化物酶体增殖物诱导的癌变。

DESCRIPTION Hypolipidemic drugs, plasticizers, and other chemicals induce hepatic peroxisome proliferation and hepatocellular carcinomas in rats and mice. Other species, however, including Syrian hamsters, guinea pigs, and primates, have a lower response to peroxisome proliferators. The mechanisms by which these agents act in some species, but not in others, are unclear, but may be related to the induction of cell proliferation, the inhibition of apoptosis, or the production of active oxygen. The production of active oxygen could lead to changes in gene expression in the cell, including the activation of NF-kB in hamsters, a non responsive species. It is therefore hypothesized that the oxidative stress is important in the carcinogenic activity of peroxisome proliferators. The investigator proposes to examine 1) the levels of cellular antioxidants and antioxidant enzymes in rat and hamster liver to determine if differential reductions occur that may explain the activation of NF-kB in rats, but not hamsters, and 2) whether other active oxygen-induced transcription factors are also differentially activated in these two species. These studies will provide information that will address the long-term objective of determining the mechanisms of peroxisome proliferator-induced carcinogenesis.