Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Sweden.
Mutagenesis. 2011 Nov;26(6):735-44. doi: 10.1093/mutage/ger041. Epub 2011 Jul 21.
In accordance with the European Parliament and Council's directive, vitamin A and C supplements can include any of four (vitamin A) or five (vitamin C) specified compounds. This study focuses on these compounds and compares their abilities to affect the DNA and viability of cells in culture, but also their potencies to chemically oxidise the DNA nucleoside deoxyguanosine (dG). To study the vitamins' strict chemical oxidation potencies, dG was exposed to vitamin solution and the amount of the oxidation product 8'-hydroxydeoxyguanosine (8-oxodG) formed was estimated using a high-performance liquid chromatography system with electrochemical and ultraviolet detection. The vitamin's ability to cause DNA damage to promyelocytic leukaemia cells (HL-60), as detected by strand breaks, alkaline labile sites and formamido pyrimidine DNA glycosylase (FPG)-sensitive sites was, after vitamin exposure, measured using the comet assay and cytotoxicity was estimated using trypan blue staining. The results highlight that vitamin A and C compounds found in supplements do have different properties, chemically as well as in a cellular system. Among the vitamin C compounds, ascorbic acid, sodium ascorbate and calcium ascorbate stood out causing both oxidation to dG and cytotoxicity to cells. The vitamin A compounds retinol, retinyl acetate and retinal (a breakdown product found in vivo) caused oxidation of dG, while retinal was the only compound causing cytotoxicity, giving rise to an almost complete cell death. β-carotene caused, as the only vitamin compound, a small increase in FPG-sensitive sites. It is concluded that even though the compounds are found under the same name (vitamin A or C), they do have different properties linked to oxidation, cytotoxicity and DNA damage.
根据欧洲议会和理事会的指令，维生素 A 和 C 补充剂可以包含四种（维生素 A）或五种（维生素 C）指定的化合物。本研究集中在这些化合物上，比较它们影响培养细胞中的 DNA 和活力的能力，以及它们化学氧化 DNA 核苷脱氧鸟苷（dG）的能力。为了研究维生素的严格化学氧化能力，将 dG 暴露于维生素溶液中，并使用具有电化学和紫外线检测的高效液相色谱系统估计形成的氧化产物 8'-羟基脱氧鸟苷（8-oxodG）的量。通过使用彗星试验测量暴露于维生素后早幼粒细胞白血病细胞（HL-60）的 DNA 断裂、碱性不稳定位点和 formamido pyrimidine DNA glycosylase（FPG）敏感位点引起的 DNA 损伤的能力，并使用台盼蓝染色估计细胞毒性。结果表明，补充剂中发现的维生素 A 和 C 化合物确实具有不同的性质，无论是在化学上还是在细胞系统中。在维生素 C 化合物中，抗坏血酸、抗坏血酸钠和抗坏血酸钙突出表现为既引起 dG 氧化又引起细胞毒性。维生素 A 化合物视黄醇、醋酸视黄酯和视网膜（体内发现的分解产物）引起 dG 氧化，而视网膜是唯一引起细胞毒性的化合物，导致几乎完全的细胞死亡。β-胡萝卜素是唯一一种引起 FPG 敏感位点略有增加的维生素化合物。结论是，即使这些化合物以相同的名称（维生素 A 或 C）存在，它们也具有与氧化、细胞毒性和 DNA 损伤相关的不同性质。
