title: Deoxycytidine glyoxal: lesion induction and evidence of repair following vitamin C supplementation in vivo.
abstract: Oxidative DNA damage is postulated to be involved in carcinogenesis, and as a consequence, dietary antioxidants have received much interest. A recent report indicates that vitamin C facilitates the decomposition of hydroperoxides in vitro, generating reactive aldehydes. We present evidence for the in vivo generation of glyoxal, an established product of lipid peroxidation, glucose/ascorbate autoxidation, or free radical attack of deoxyribose, following supplementation of volunteers with 400 mg/d vitamin C. Utilizing a monoclonal antibody to a deoxycytidine-glyoxal adduct (gdC), we measured DNA lesion levels in peripheral blood mononuclear cells. Supplementation resulted in significant (p =.001) increases in gdC levels at weeks 11, 16, and 21, with corresponding increases in plasma malondialdehyde levels and, coupled with previous findings, is strongly suggestive of a pro-oxidative effect. However, continued supplementation revealed a highly significant (p =.0001) reduction in gdC levels. Simultaneous analysis of cyclobutane thymine dimers revealed no increase upon supplementation but, as with gdC, levels decreased. Although no single mechanism is identified, our data demonstrate a pro-oxidant event in the generation of reactive aldehydes following vitamin C supplementation in vivo. These results are also consistent with our hypothesis for a role of vitamin C in an adaptive/repair response and indicate that nucleotide excision repair specifically may be affected.
authors.affiliation: Oxidative Stress Group, Department of Clinical Biochemistry, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK. msc5@le.ac.uk
authors.forename: Marcus S
authors.initials: MS
authors.lastname: Cooke
authors.forename: Nalini
authors.initials: N
authors.lastname: Mistry
authors.forename: Jabeen
authors.initials: J
authors.lastname: Ahmad
authors.forename: Helen
authors.initials: H
authors.lastname: Waller
authors.forename: Lynda
authors.initials: L
authors.lastname: Langford
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Bevan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Evans
authors.forename: George D D
authors.initials: GD
authors.lastname: Jones
authors.forename: Karl E
authors.initials: KE
authors.lastname: Herbert
authors.forename: Helen R
authors.initials: HR
authors.lastname: Griffiths
authors.forename: Joseph
authors.initials: J
authors.lastname: Lunec
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D003841:Deoxycytidine / Q000097:blood / Q000378:metabolism*; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006037:Glyoxal / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011740:Pyrimidine Dimers / Q000097:blood / Q000652:urine; D013997:Time Factors
chemical_list: D018736:DNA Adducts; D011740:Pyrimidine Dimers; D003841:Deoxycytidine; D008315:Malondialdehyde; D006037:Glyoxal; D001205:Ascorbic Acid