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淋巴细胞中的DNA损伤及对氧化损伤的易感性:类胡萝卜素在体内外的作用

DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoids in vitro and in vivo.

作者信息

Astley Siân B, Hughes David A, Wright Anthony J A, Elliott Ruan M, Southon Susan

机构信息

Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.

出版信息

Br J Nutr. 2004 Jan;91(1):53-61. doi: 10.1079/bjn20031028.

Abstract

Reports on the effects of carotenoids are conflicting. The present paper examines similarities and differences from contiguous studies in vitro and in vivo. Single-cell gel electrophoresis was used to measure the frequency of single-strand breaks (SSB) in the cell line MOLT-17 (as a model system) and human peripheral blood lymphocytes (PBL). MOLT-17 cells were supplemented with beta-carotene, lutein or lycopene at a range of concentrations (0.00-8.00 micromol/l) using a liposome delivery method. Uptake was dose-dependent. beta-Carotene concentration in the media had no effect on SSB in control cells, but incubation with lycopene or lutein (>2.00 micromol/l) increased the numbers of SSB in control cells. MOLT-17 DNA was less susceptible to oxidative damage (100 micromol H2O2/l, 5 min, 4 degrees C) following incubation with carotenoids between 0.50 and 1.00 micromol/l; at >1.00 micromol/l the effects were ambiguous. Apparently healthy male volunteers supplemented their habitual diets with lutein, beta-carotene or lycopene (natural isolate capsules, 15 mg/d, 4 weeks) in three independent studies, raising plasma concentrations to different extents. Lycopene and lutein had no effect on SSB in control PBL or following oxidative challenge. However, increased plasma beta-carotene was associated with more SSB in control cells whilst PBL DNA resistance to oxidative damage ex vivo was unaffected. These results suggest that the carotenoids are capable of exerting two overlapping but distinct effects: antioxidant protection by scavenging DNA-damaging free radicals and modulation of DNA repair mechanisms.

摘要

关于类胡萝卜素作用的报告相互矛盾。本文研究了体外和体内连续研究中的异同。采用单细胞凝胶电泳法测量MOLT-17细胞系(作为模型系统)和人外周血淋巴细胞(PBL)中单链断裂(SSB)的频率。使用脂质体递送方法,以一系列浓度(0.00 - 8.00微摩尔/升)向MOLT-17细胞补充β-胡萝卜素、叶黄素或番茄红素。摄取呈剂量依赖性。培养基中β-胡萝卜素浓度对对照细胞中的SSB无影响,但与番茄红素或叶黄素(>2.00微摩尔/升)孵育会增加对照细胞中的SSB数量。在0.50至1.00微摩尔/升之间与类胡萝卜素孵育后,MOLT-17 DNA对氧化损伤(100微摩尔过氧化氢/升,5分钟,4℃)的敏感性较低;浓度>1.00微摩尔/升时,效果不明确。在三项独立研究中,明显健康的男性志愿者在其日常饮食中补充叶黄素、β-胡萝卜素或番茄红素(天然分离胶囊,15毫克/天,4周),使血浆浓度有不同程度的升高。番茄红素和叶黄素对对照PBL中的SSB或氧化应激后均无影响。然而,血浆β-胡萝卜素升高与对照细胞中更多的SSB相关,而PBL DNA离体对氧化损伤的抗性未受影响。这些结果表明,类胡萝卜素能够发挥两种重叠但不同的作用:通过清除损伤DNA的自由基进行抗氧化保护以及调节DNA修复机制。

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