Handbook of Vitamin C Research

52Yasuo Kagawa, Shizu Higasa, Masaru Tsujimura et al.mg/day) is necessary to overcome the toxic effects of xenobiotics. Oral administration of asingle dose of 1- 14 C-AsA revealed that smokers had a higher metabolic turnover (140mg/day) than nonsmokers (100 mg/day) to reach steady-state concentrations and that totalbody pools were comparable to those in nonsmokers [42]. Cigarette smoke carcinogens areremoved in Phase 2 detoxification by the glutathione S-transferase (GST) superfamily, ofwhich GSTP1 is most strongly expressed as GST in the lung and other tissues [36, 37]. VCis known to prevent DNA mutation induced by both xenobiotics and ROS [16, 34]. The linkbetween genome damage and adverse health outcomes is compelling. There is increasingevidence indicating that genome instability, in the absence of overt exposure to xenobiotics,is itself a sensitive marker of nutritional deficiency. Intake of VC above RDA is associatedwith reduced tissue damage [11, 14, 16]. Nutrigenomics of VC is an emerging and importantnew field of nutritional science because it is increasingly evident that optimal concentrationof VC for the prevention of tissue damage is dependent on genetic polymorphisms that alterthe function of genes involved directly or indirectly in DNA repair and metabolism [31].(5) The Outline of Discussions on the ResultsGenetic polymorphisms related to xenobiotic or oxidative stress may thus causeinterindividual differences in VC requirements [3-9]. After presenting our experimental datain the Results section, the roles of VC as an antioxidant [1,10, 11], especially in the light ofhuman specific VC metabolism (section 1), VC transport [26, 40, 43, 44] (section 2), DAsAreduction [23, 45-49] (section 3), effects of genetic polymorphisms on AsA and DAsAmetabolism [5, 8, 50] (section 4), delactonization of DAsA by dehydroascobatase [3, 46] andsenescence marker protein 30 (SMP 30) [51-57] (section 5), monodehydroascorbate radicals(section 6), pro-oxidant activities of VC [20, 21] (section 7), the evolutional origin of humanspecific VC-related gene structure [25-27] (section 8), and finally, RDAs [28, 29] andoptimal human nutrition of VC [31] will be discussed (section 9) after summarizing theeffects of genetic polymorphisms [5, 58, 59] and xenobiotics on AsA and DAsA metabolism[31].(1) SubjectsMaterials and MethodsA. Japanese group A for analysis of gene variant frequency and preliminary VC levelexperiments comprised 211 healthy Japanese women (aged 21 - 22 years) and their dietaryintake of VC was assessed by 3-day weighted food record, as reported previously [6]. Thesubject numbers in group A for determining gene variant frequencies were (n = 211 forSOD2; n = 209 for SOD3; n = 210 for GSTP1-1; and n = 210 for GSTP1-2) [59].B. Japanese group B for VC-loading experiments comprised healthy female universitystudents (n = 17; age, 21.0 ± 1.1 y; height, 157.0 ± 5.8 cm; weight, 53.0 ± 7.0 kg; body massindex; 21.0 ± 2.7) [4]. Average values on blood analysis were all within the normal limits, as