Department of Epidemiology, Prevention and Special Functions, National Institute for Cancer Research (IST), Genova, Italy.
J Biomed Sci. 2010 Jul 28;17(1):63. doi: 10.1186/1423-0127-17-63.
Whether microgravity might influence tumour growth and carcinogenesis is still an open issue. It is not clear also if and how normal and transformed cells are differently solicited by microgravity. The present study was designed to verify this issue.
Two normal, LB and HSC93, and two transformed, Jurkat and 1310, lymphoblast cell lines were used as representative for the two conditions. Two lymphoblast lines from Fanconi's anemia patients group A and C (FA-A and FA-C, respectively), along with their isogenic corrected counterparts (FA-A-cor and FA-C-cor) were also used. Cell lines were evaluated for their proliferative ability, vitality and apoptotic susceptibility upon microgravity exposure in comparison with unexposed cells. Different parameters correlated to energy metabolism, glucose consumption, mitochondrial membrane potential (MMP), intracellular ATP content, red-ox balance and ability of the cells to repair the DNA damage product 8-OHdG induced by the treatment of the cells with 20 mM KBrO3 were also evaluated.
Transformed Jurkat and 1310 cells appear resistant to the microgravitational challenge. On the contrary normal LB and HSC93 cells display increased apoptotic susceptibility, shortage of energy storages and reduced ability to cope with oxidative stress. FA-A and FA-C cells appear resistant to microgravity exposure, analogously to transformed cells. FA corrected cells did shown intermediate sensitivity to microgravity exposure suggesting that genetic correction does not completely reverts cellular phenotype.
In the light of the reported results microgravity should be regarded as an harmful condition either when considering normal as well as transformed cells. Modeled microgravity and space-based technology are interesting tools in the biomedicine laboratory and offer an original, useful and unique approach in the study of cellular biochemistry and in the regulation of metabolic pathways.
微重力是否会影响肿瘤生长和癌变仍是一个悬而未决的问题。目前也不清楚正常细胞和转化细胞是否会受到微重力的不同影响,以及如何受到影响。本研究旨在验证这一问题。
使用两种正常的 LB 和 HSC93 以及两种转化的 Jurkat 和 1310 淋巴母细胞系作为两种状态的代表。还使用了来自范可尼贫血患者组 A 和 C(FA-A 和 FA-C)的两种淋巴母细胞系,以及它们的同源校正对应物(FA-A-cor 和 FA-C-cor)。与未暴露细胞相比,评估细胞系在暴露于微重力下时的增殖能力、活力和凋亡易感性。还评估了与能量代谢、葡萄糖消耗、线粒体膜电位(MMP)、细胞内 ATP 含量、氧化还原平衡以及细胞修复由 20mM KBrO3 处理细胞引起的 DNA 损伤产物 8-OHdG 的能力相关的不同参数。
转化的 Jurkat 和 1310 细胞对微重力挑战具有抗性。相反,正常的 LB 和 HSC93 细胞显示出增加的凋亡易感性、能量储存不足和降低的应对氧化应激的能力。FA-A 和 FA-C 细胞对微重力暴露具有抗性,类似于转化细胞。FA 校正细胞对微重力暴露显示出中间敏感性,表明遗传校正并不能完全逆转细胞表型。
根据报告的结果,微重力应被视为一种有害条件,无论是考虑正常细胞还是转化细胞。模拟微重力和基于空间的技术是生物医学实验室中有趣的工具,为细胞生物化学研究和代谢途径调节提供了一种原始、有用和独特的方法。