Forsyth Nicholas R, Evans A Patrice, Shay Jerry W, Wright Woodring E
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
Aging Cell. 2003 Oct;2(5):235-43. doi: 10.1046/j.1474-9728.2003.00057.x.
The role of ambient (21%) and physiological oxygen (2-5%) in the immortalization of fetal vs. adult human lung fibroblasts was examined. Growth in low oxygen and antioxidants extended the lifespan of both fetal and adult strains. As the ectopic expression of telomerase could immortalize adult lung fibroblasts cultured in ambient oxygen, the lifespan-shortening effects of 21% oxygen must have been largely limited to telomeres. By contrast, fetal lung fibroblasts could not be immortalized in ambient oxygen in spite of telomere elongation by telomerase, suggesting more widespread oxidative damage. The long-term culture requirements for the immortalization of WI-38 fetal lung fibroblasts included supplementation with N-(tert) butyl hydroxylamine, dexamethasone, zinc and vitamin B12, in addition to growth in physiological oxygen. The mechanisms regulating telomere shortening remain controversial. The present results suggest that both end-replication and oxidative damage events contribute to telomere shortening in lung fibroblasts in vitro. These observations emphasize the need for better analytical techniques to distinguish whether the correlation of short telomeres with disease and mortality in humans reflects the consequences of increased proliferation, telomere shortening as a result of oxidative damage or some combination of these processes.
研究了环境氧（21%）和生理氧（2 - 5%）在人胎儿与成人肺成纤维细胞永生化过程中的作用。在低氧环境及添加抗氧化剂的条件下培养，胎儿和成体菌株的寿命均得以延长。由于端粒酶的异位表达可使在环境氧条件下培养的成人肺成纤维细胞永生化，因此21%氧的寿命缩短效应必定在很大程度上限于端粒。相比之下，尽管端粒酶可使胎儿肺成纤维细胞的端粒延长，但在环境氧条件下却无法使其永生化，这表明存在更广泛 的氧化损伤。WI - 38胎儿肺成纤维细胞永生化的长期培养条件除了要在生理氧环境中生长外，还包括添加N -（叔）丁基羟胺、地塞米松、锌和维生素B12。调节端粒缩短的机制仍存在争议。目前的结果表明，末端复制和氧化损伤事件均有助于体外肺成纤维细胞中端粒的缩短。这些观察结果强调需要更好的分析技术，以区分人类端粒缩短与疾病和死亡率之间的相关性，是反映了增殖增加的后果、氧化损伤导致的端粒缩短，还是这些过程的某种组合。
