Handbook of Vitamin C Research

162Borut Poljsak and John G. Ionescug dose of vitamin C neither caused DNA damage nor protected cells against hydrogenperoxide-induced toxicity. Two other studies measured DNA chromosome damage aftertreatment of lymphocytes with bleomycin, a test for genetic instability. Following vitamin Csupplementation for two weeks, Pohl and Reidy (1989) found decreased chromosome breaksand Anderson et al. (1997) reported no effects on DNA damage but increased chromosomeaberrations. Since the findings of these studies were inconsistent, ex vivo damage cannot beused to estimate a vitamin C requirement (DRI for vitamin C, Food and Nutrition Board,Institute of Medicine 2000).A study using rats challenged with paraquat showed an antioxidant role for vitamin Cwhen given before paraquat treatment, but a pro-oxidant role when given after the challenge,as determined by expiratory ethane (Kang et al. 1998). Similar effect was reported by Poljsaket al. (1995) on vitamin C pre-treated yeast cells which were later exposed to chromium.Additionally, pretreatment of Chinese hamster V-79 cells with ascorbic acid enhancedthe cytotoxicity of chromate and enhanced the DNA-protein cross-links (Sugiyama et al.1991b). A study conducted by Quievryn et al. (2002) showed that increasing intracellularascorbate levels by pretreating cultures with dehydroascorbic acid (DHA) significantlyincreased Asc-DNA crosslink levels. O'Brien et al. (2002) found that increasing the molarratio of ascorbate to Cr(VI) beyond 2 led to a general reduction in Cr-DNA adducts, becauseat these higher relative levels of ascorbate, more coordinate sites on Cr are occupied byascorbate and, thus, prevent further Cr-DNA interaction. Moreover, reactive ascorbyl andcarbon-based radicals are generated at ratios of above or below 3, respectively. At anAsc:Cr(VI) ratio of 12, fewer ICLs were observed compared to the ratio of 0.5, suggestingthat higher relative molar amounts of Asc interfere with the formation of both, mono and bifunctionaladducts (O'Brien et al. 2002). Another animal study has reported an antioxidantrole for vitamin C in guinea pigs co-supplemented with vitamin C and iron. In the study ofCollins et al. (1997) autoxidation of liver microsomes obtained from iron-supplementedguinea pigs resulted in increased accumulation of MDA compared with control animals oranimals co-supplemented with iron and vitamin C. An important point to note about studiesin animals that can synthesize vitamin C, such as rats, is that the results may not reflect thesituation in humans. According to Carr and Frei (1999) several vitamin C and iron cosupplementationstudies, both in animals and humans, indicate that vitamin C inhibits ratherthan promotes iron-dependent oxidative damage. Similarly, a study carried out in humans toassess the effects of simultaneous iron and vitamin C supplementation has yielded mixedresults with respect to various types of oxidized DNA bases in leukocytes. Reanalysis of thedata from this study (Rehman et al. 1998) suggest that vitamin C acts as an antioxidant, ratherthan a pro-oxidant, in vivo in the presence of iron (Carr and Frei 1999).Although vitamin C induced Fenton chemistry occurs readily in vitro, its relevance invivo has been a matter of some controversy, the main point of contention being theavailability of catalytic metal ions in vivo (Halliwell and Gutteridge 1986). It has yet to beproven that oxidative damage in vivo can be ameliorated by supplementation with large dosesof ascorbic acid. The dose of ascorbate which is protective in vitro, may not be relevant invivo (Griffiths 2001). According to Simopoulos (1993), for genetic reasons more than 10% ofAmerican whites and perhaps as many as 30% of American blacks have high body iron.Vitamin C is known to increase the gastrointestinal absorption of nonheme iron by reducing