Okai Y, Higashi-Okai K, Machida K, Nakamura H, Nakayama K, Fujita K, Tanaka T, Otani S, Taniguchi M
Department of Human Life Science, Osaka Kun-Ei Women's College, Showjaku, Set's City, Osaka, Japan.
FEMS Microbiol Lett. 2000 Apr 1;185(1):65-70. doi: 10.1111/j.1574-6968.2000.tb09041.x.
The cell growth-modulating activity of an endocrine disruptor, p-nonylphenol (NP), was estimated using the yeast Saccharomyces cerevisiae as a simple model of eukaryotic cells. NP caused a dose-dependent suppressive effect on cell growth of S. cerevisiae at 10, 25 and 50 microM. The NP-induced cell growth inhibition was restored when concomitantly lipophilic antioxidants such as alpha-tocopherol and beta-carotene were supplied, but not the hydrophilic antioxidants ascorbic acid or (-)epigallocatechin gallate (EGCG). The cellular oxygen consumption of S. cerevisiae was also inhibited in a dose-dependent fashion by the extracellular addition of NP, and pretreatment with alpha-tocopherol and beta-carotene suppressed NP-induced inhibition of cellular oxygen consumption, but ascorbic acid and EGCG were not effective. Furthermore, NP caused a marked generation of radical oxygen species (ROS) in S. cerevisiae, which was suppressed by treatment with alpha-tocopherol and beta-carotene, but not with ascorbic acid and EGCG. However, NP did not show a significant inhibitory effect on cell growth and survival of mitochondria-deficient petite mutant cells and they showed a relatively weak ROS-generating activity compared with parent yeast cells. These results suggest that NP-induced inhibition of cell growth and oxygen consumption in S. cerevisiae might be possibly associated with ROS generation in yeast mitochondria. The significance of this finding is discussed from the viewpoint of NP-induced oxidative stress against eukaryotic cells.
使用酿酒酵母作为真核细胞的简单模型，评估了内分泌干扰物对壬基酚（NP）的细胞生长调节活性。在10、25和50微摩尔浓度下，NP对酿酒酵母的细胞生长产生剂量依赖性抑制作用。当同时提供亲脂性抗氧化剂如α-生育酚和β-胡萝卜素时，NP诱导的细胞生长抑制得以恢复，但亲水性抗氧化剂抗坏血酸或（-）表没食子儿茶素没食子酸酯（EGCG）则无效。通过在细胞外添加NP，酿酒酵母的细胞耗氧量也呈剂量依赖性受到抑制，用α-生育酚和β-胡萝卜素预处理可抑制NP诱导的细胞耗氧量抑制，但抗坏血酸和EGCG无效。此外，NP在酿酒酵母中引起明显的活性氧（ROS）生成，用α-生育酚和β-胡萝卜素处理可抑制该生成，但抗坏血酸和EGCG则无效。然而，NP对线粒体缺陷型小菌落突变细胞的细胞生长和存活未显示出显著抑制作用，与亲代酵母细胞相比，它们的ROS生成活性相对较弱。这些结果表明，NP诱导的酿酒酵母细胞生长抑制和耗氧量抑制可能与酵母线粒体中的ROS生成有关。从NP诱导的针对真核细胞的氧化应激角度讨论了这一发现的意义。
