Deoxycytidine glyoxal:Lesion induction and evidence of repair following vitamin C supplementation in vivo

Cooke, Marcus S., Mistry, Nalini, Ahmad, Jabeen, Waller, Helen, Langford, Lynda, Bevan, Ruth J., Evans, Mark D., Jones, George D.D., Herbert, Karl E., Griffiths, Helen R. and Lunec, Joseph (2003). Deoxycytidine glyoxal:Lesion induction and evidence of repair following vitamin C supplementation in vivo. Free Radical Biology and Medicine, 34 (2), pp. 218-225.

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. © 2003 Elsevier Science Inc.

Publication DOI: https://doi.org/10.1016/S0891-5849(02)01240-6
Divisions: Languages & Social Sciences > French
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Life & Health Sciences > Biomedical Sciences research group
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Uncontrolled Keywords: deoxycytidine-glyoxal,DNA damage,DNA repair,free radicals,lipid hydroperoxide,monoclonal antibody,oxidative,Medicine(all),Toxicology,Clinical Biochemistry
Published Date: 2003-01-15

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