Merinas-Amo Tania, Tasset-Cuevas Inmaculada, Díaz-Carretero Antonio M, Alonso-Moraga Ángeles, Calahorro Fernando
1 Department of Genetics, University of Córdoba , Córdoba, Spain .
2 Department of Developmental and Molecular Biology, Yeshiva University Albert Einstein College , New York, New York, USA .
J Med Food. 2017 Mar;20(3):223-234. doi: 10.1089/jmf.2016.0075. Epub 2017 Jan 19.
The purpose of the present study was to examine the nutraceutical potential of choline as an added value to its well-known brain nutrient role. Several toxicity, antitoxicity, genotoxicity, antigenotoxicity, and longevity endpoints were checked in the somatic mutation and recombination test in in vivo Drosophila animal model. Cytotoxicity in human leukemia-60 cell line (HL-60) promyelocytic and NIH3T3 mouse fibroblast cells, proapoptotic DNA fragmentation, comet assay, methylation status, and macroautophagy (MA) activity were tested in in vitro assays. Choline is not only safe but it is also able to protect against the DNA damage caused by an oxidative genotoxin. Moreover, it improves the life extension in the animal model. The in vitro results show that it is able to exhibit genetic damage against leukemia HL-60 cells. Single-strand breaks in DNA are observed at the molecular level in treatments with choline, although only a significant hypermethylation on the long interspersed elements-1 and a hypomethylation on the satellite-alpha DNA repetitive DNA sequences of HL-60 cells at the lowest concentration (0.447 mM) were observed. Besides, choline decreased MA at the lower assayed concentration and the MA response to topoisomerase inhibitor (etoposide) is maintained in the presence of treatment with 0.22 mM choline. Taking into account the hopeful results obtained in the in vivo and in vitro assays, choline could be proposed as a substance with an important nutraceutical value for different purposes.
本研究的目的是检验胆碱作为一种营养保健品的潜力,这是其著名的脑营养作用之外的附加价值。在体内果蝇动物模型的体细胞突变和重组试验中,检查了几个毒性、抗毒性、遗传毒性、抗遗传毒性和寿命终点指标。在体外试验中,检测了人白血病-60细胞系(HL-60)早幼粒细胞和NIH3T3小鼠成纤维细胞的细胞毒性、促凋亡DNA片段化、彗星试验、甲基化状态和巨自噬(MA)活性。胆碱不仅安全,而且能够保护细胞免受氧化基因毒素造成的DNA损伤。此外,它还能延长动物模型的寿命。体外试验结果表明,它能够对白血病HL-60细胞造成遗传损伤。在胆碱处理中,在分子水平上观察到DNA单链断裂,不过仅在最低浓度(0.447 mM)时,观察到HL-60细胞的长散在元件-1上有显著的高甲基化以及卫星α DNA重复DNA序列上有低甲基化。此外,胆碱在较低检测浓度下降低了巨自噬,并且在存在0.22 mM胆碱处理的情况下,巨自噬对拓扑异构酶抑制剂(依托泊苷)的反应得以维持。考虑到在体内和体外试验中获得的有希望的结果,胆碱可被认为是一种具有重要营养保健价值、可用于不同目的的物质。