Aarsaether N, Aarsland A, Kryvi H, Nilsson A, Svardal A, Ueland P M, Berge R K
Laboratory of Clinical Biochemistry, University of Bergen, Norway.
Carcinogenesis. 1989 Jun;10(6):987-94. doi: 10.1093/carcin/10.6.987.
Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal beta-oxidation, carnitine palmitoyltransferase and omega-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were increased, whereas the peroxisomal and cytosolic activities were decreased. Ethionine administration decreased the catalase and urate oxidase activities in both a dose- and time-related manner. The liver cells and the volume fraction of cytoplasma decreased 40% in ethionine-exposed animals, whereas the average nuclei volume fraction increased approximately 50%. The volume fraction and the total number of mitochondria increased 1.5-fold after ethionine exposure and an accumulation of lipid in large droplets of the hepatocytes was observed. No proliferation of peroxisomes was observed after treatment; the volume fraction and the number of peroxisomes decreased. However, the size of peroxisomes in livers of ethionine-exposed rats tended to be greater than controls; a 1.5-fold increase in average size was observed. As there was no induction of the protein content of the bifunctional enoyl-CoA hydratase, an enzyme involved in peroxisomal beta-oxidation, it is considered that ethionine selectively stimulates the peroxisomal beta-oxidation due to increased peroxisome surface area rather than evoked a peroxisome proliferation capacity. Increased peroxisomal beta-oxidation was also observed in the kidney of ethionine-exposed rats at a dose of 750 mg/day/kg body weight. At that dose the amount of reduced glutathione (GSH) was significantly increased in kidney. The amount of GSH and the level of peroxisomal beta-oxidation were significantly increased in liver at an ethionine dose of 100 mg/day/kg body weight. These responses in liver were evident within 2 days of ethionine exposure and then leveled off whereas a significant increase in GSH and peroxisomal beta-oxidation in kidney was observed within 12 days. Whether the acute H2O2-generating peroxisomal oxidation of long-chain fatty acids in the liver may also make this organ susceptible to the long-term effects of low-dose ethionine and be an important step in the chain of events which eventually results in tumour development should be considered.
给予乙硫氨酸会导致过氧化物酶体β-氧化、肉碱棕榈酰转移酶和ω-氧化活性呈剂量和时间依赖性增强，尤其是月桂酸的12-羟基化。线粒体尤其是微粒体棕榈酰辅酶A水解酶活性增加，而过氧化物酶体和胞质溶胶活性降低。给予乙硫氨酸会使过氧化氢酶和尿酸氧化酶活性以剂量和时间相关的方式降低。在接触乙硫氨酸的动物中，肝细胞和细胞质的体积分数减少了40%，而平均细胞核体积分数增加了约50%。接触乙硫氨酸后线粒体的体积分数和总数增加了1.5倍，并且观察到肝细胞的大脂滴中有脂质积累。处理后未观察到过氧化物酶体增殖；过氧化物酶体的体积分数和数量减少。然而，接触乙硫氨酸的大鼠肝脏中过氧化物酶体的大小往往大于对照组；观察到平均大小增加了1.5倍。由于参与过氧化物酶体β-氧化的双功能烯酰辅酶A水合酶的蛋白质含量未被诱导，因此认为乙硫氨酸是由于过氧化物酶体表面积增加而选择性刺激过氧化物酶体β-氧化，而不是引发过氧化物酶体增殖能力。在接触乙硫氨酸的大鼠肾脏中，当剂量为750mg/天/千克体重时也观察到过氧化物酶体β-氧化增加。在该剂量下，肾脏中还原型谷胱甘肽（GSH）的量显著增加。当乙硫氨酸剂量为100mg/天/千克体重时，肝脏中GSH的量和过氧化物酶体β-氧化水平显著增加。肝脏中的这些反应在接触乙硫氨酸后2天内明显，然后趋于平稳，而在12天内观察到肾脏中GSH和过氧化物酶体β-氧化显著增加。肝脏中长链脂肪酸的急性产H2O2过氧化物酶体氧化是否也会使该器官易受低剂量乙硫氨酸的长期影响，并且是否是最终导致肿瘤发生的一系列事件中的重要一步，这一点应该予以考虑。
