On the cytotoxicity of vitamin C and metal ions

Abstract

The toxicity of ascorbate towards phage lambda and the phages T2-T7 has been investigated. At room temperature the T-odd and lambda bacteriophages are highly susceptible to ascorbate-induced damage, whereas the T-even phages are practically resistant. The toxicity of ascorbate is dependent on the presence of copper (or iron) and oxygen, although oxygen is not required in the presence of H,O,. Hydrogen peroxide is essential for the ascorbateinduced phage inactivation and the damage is prevented by catalase. At the concentrations used, most of the copper ions are bound to the phage particles. Chelating agents such as EDTA or histidine fully protect the phages, whereas salicylate only reduces the rate of phage inactivation. OH scavengers such as sucrose, formate, mannitol, terf-butyl alcohol or poly(ethy1ene glycol) have no protective effect.Experiments with DNA labeled phages indicate that both phage adsorption and DNA injection are impaired as a result of the exposure to ascorbate and copper. The failure to express the viral genetic information as a result of single and double-strand breaks in the DNA, probably also contribute to the loss of the plaque-forming ability of the phages.The results are interpreted in terms of a 'site-specific' Fenton mechanism according to which the binding of the transition metal ions to the biological target is a prerequisite for the production of damage. The bound metal ion is reduced either by q, ascorbate or other reductants and is subsequently reoxidized by H,O, yielding OH' radicals.This cyclic redox reaction of the metal generates OH' radicals which react with vital macromolecules with a high probability of causing 'multi-hit' damage. This 'site-specific' formation of OH' radicals, which takes place near the target molecules, accounts both for the high damaging efficiency and for the failure of OH' scavengers to protect against it.

Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

“…However, the benefits of ascorbic acid prophylaxis remain equivocal, with human studies demonstrating an improvement [9], no change [10], or an increase in ROS and subsequent deterioration in vascular function [11,12]. Concerns have been raised about the administration of ascorbic acid in the presence of redoxactive transition metal ions, since ascorbate can reduce transition metal ions and catalyse the Fenton-driven generation of hydroxyl and alkoxyl radicals in vitro [13]. Although the thermodynamics of this reaction in vivo remain controversial [14], an acute bout of physical exercise has been shown to liberate extracellular 'catalytic' iron [15] that, in the presence of supplementary ascorbic acid, may potentially compound the generation of ROS [16].…”

Mobilization of iron from cellular ferritin by ascorbic acid in neuroblastoma SK‐N‐SH cells: an EPR study

“…Further work demonstrated that ascorbic acid induces DNA strand breaks in neuroblastoma cells [25,26] and tissues [27]. These effects were especially pronounced in the presence of small amounts of H202 and transition metals like iron [28,29]. Therefore, oxidative damage in neuroblastoma cells may be supported by an initial reductive release of iron from the large ferritin pool [11,12] and by high amounts of intracellularly produced H202 [26,30].…”

A Review of the Nature and Effectiveness of Nutrition Interventions in Adult Males: A Guide for Intervention Strategies

“…The reduction of iron by ascorbic acid has been suggested to increase dietary absorption of non-heme iron [26]. It is well known that in the presence of redox-active iron, ascorbic acid acts as a pro-oxidant in vitro and might contribute to the formation of hydroxyl radical, which eventually may lead to lipid, DNA or protein oxidation [27]. Thus, ascorbic acid supplementation in individuals with high iron and or bleomycindetectable iron (BDI) in some preterm infants could be deleterious because it may cause oxidative damage to biomolecules [28][29][30][31].…”