Mizumoto Y, Nakae D, Yoshiji H, Andoh N, Horiguchi K, Endoh T, Kobayashi E, Tsujiuchi T, Shimoji N, Denda A
Department of Oncological Pathology, Nara Medical University, Japan.
Carcinogenesis. 1994 Feb;15(2):241-6. doi: 10.1093/carcin/15.2.241.
Effects of a lipophilic derivative of vitamin C, 2-O-octadecylascorbic acid (CV-3611), as well as its parent L-ascorbic acid (AscA), DL-alpha-tocopherol (alpha-T) and its hydrophilic derivative, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), on the number and size of gamma-glutamyltransferase (GGT)-positive putative preneoplastic lesions were examined and compared with their influences on 8-hydroxyguanine formation in DNA and 2-thiobarbituric acid-reacting substance generation in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks. A total of 90 male Fischer 344 rats, 6 weeks old, were divided into 18 groups each consisting of five rats. Group 1 received the CDAA diet alone; Groups 2, 3 and 4 received the CDAA diet containing respectively 0.01, 0.05 and 0.10% CV-3611; Groups 5-7, 8-10 and 11-13 similarly received the CDAA diet containing AscA, alpha-T and Trolox, respectively, at these same low, middle and high concentrations; Group 14 received a choline-supplemented, L-amino acid-defined (CSAA) diet alone; Groups 15-18 were given the CSAA diet containing CV-3611, AscA, alpha-T and Trolox, respectively, all at the 0.10% level. While all four vitamin derivatives exerted inhibitory effects on all four parameters, in each case dose-dependently, CV-3611 demonstrated the most pronounced effects. The present results indicated that lipophilic vitamin C derivatives may be particularly effective chemopreventive agents against CDAA diet-associated, oxidative stress-related hepatocarcinogenesis via its superior antioxidative properties.
研究了维生素C的亲脂性衍生物2-O-十八烷基抗坏血酸（CV-3611）及其母体L-抗坏血酸（AscA）、DL-α-生育酚（α-T）及其亲水性衍生物6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-羧酸（Trolox）对γ-谷氨酰转移酶（GGT）阳性的潜在癌前病变数量和大小的影响，并将其与它们对喂食胆碱缺乏、L-氨基酸限定（CDAA）饮食12周的大鼠肝脏中DNA中8-羟基鸟嘌呤形成和2-硫代巴比妥酸反应物质生成的影响进行比较。总共90只6周龄的雄性Fischer 344大鼠被分成18组，每组五只。第1组仅接受CDAA饮食；第2、3和4组分别接受含0.01%、0.05%和0.10%CV-3611的CDAA饮食；第5-7组、8-10组和11-13组同样分别接受含AscA、α-T和Trolox的CDAA饮食，浓度分别为相同的低、中、高浓度；第14组仅接受补充胆碱的L-氨基酸限定（CSAA）饮食；第15-18组分别接受含CV-3611、AscA、α-T和Trolox的CSAA饮食，浓度均为0.10%。虽然所有四种维生素衍生物对所有四个参数均有抑制作用，且在每种情况下均呈剂量依赖性，但CV-3611的作用最为显著。目前的结果表明，亲脂性维生素C衍生物可能因其卓越的抗氧化性能，成为预防与CDAA饮食相关的、氧化应激相关肝癌发生的特别有效的化学预防剂。
