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
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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