Double Lesions are Produced in DNA Oligomer by Ionizing Radiation and by Metal-Catalyzed H₂O₂Reactions

Abstract

It was demonstrated previously that double lesions are produced in DNA by ionizing radiation. These double lesions consist of adjacent nucleotides each bearing a modified base. The goal of the present investigation was to determine whether Fenton chemistry can generate the same kind of lesions. DNA oligomers were exposed to metal-catalyzed H(2)O(2) reactions, and the products were characterized by chromatography and by mass spectrometry. Double lesions are produced by this treatment in which deoxyguanosine is oxidized to 8-oxo-7,8-dihydrodeoxyguanosine and an adjacent pyrimidine nucleoside is degraded to a formamido remnant.

Ozone-Induced DNA Damage: A Pandora’s Box of Oxidatively Modified DNA Bases

“…Tandem lesions containing N -formamide and 8oxoG have previously been characterized and detected in oligonucleotides and isolated DNA exposed to ionizing radiation and Fenton-like reactions implying the generation of hydroxyl radicals. ,,,, The mechanism of formation of these and other tandem lesions has been proposed to involve initial attack of • OH and incorporation of oxygen to form peroxyl radicals, which subsequently react with the adjacent G moiety to form either 8oxoG or 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). , A similar mechanism may be responsible for the formation of tandem lesions by ozone. In addition to the reaction pathway involving a bipolar carbonyl intermediate (analogous to I → II ), Pryor proposed O–O bond homolysis of the initial ozonide into a biradical species to explain the effects of temperature, metal chelators, and H 2 O on the formation of radical species during ozone-mediated oxidation of a biological target .…”

Chromosomal rearrangement as the basis for human tumourigenesis

“…The ability of naturally occurring levels of endogenous or exogenous DNA damaging agents (other than ionizing radiation and radiomimetics) to induce complex lesions in human cells is questionable. However, single eOH radicals, which can be generated by Fenton-type reactions involving a redox-active transition metal ion such as iron(II) and the reactive oxygen species (ROS) hydrogen peroxide, can induce tandem base modifications in which 7,8-dihydro-8-oxoguanine is flanked by a pyrimidine nucleoside whose base has been degraded to a formamido remnant (Patrzyc et al 2001). Little is known about the repair of such lesions, although there are data suggesting that some nucleases have difficulty in hydrolysing formamido residues (Bourdat et al 1999.…”

Long-Term Intake of High Doses of Vitamin C Down-regulates Anti-oxidant Enzymes in Human Erythrocytes

“…Because of their high reactivity, they can damage major cellular components such as lipids (1), proteins (2) and nucleic acids (3). Aerobic organisms remove ROS by using enzymes (4) such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd) and glutathione-s-transferase (GST) and non-protein anti-oxidants (5) such as vitamins C, E, β-carotene and polyphenols.…”