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

Marcus S. Cooke*, Nalini Mistry, Jabeen Ahmad, Helen Waller, Lynda Langford, Ruth J. Bevan, Mark D. Evans, George D.D. Jones, Karl E. Herbert, Helen R. Griffiths, Joseph Lunec

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)218-225
Number of pages8
JournalFree Radical Biology and Medicine
Volume34
Issue number2
DOIs
Publication statusPublished - 15 Jan 2003

Keywords

  • deoxycytidine-glyoxal
  • DNA damage
  • DNA repair
  • free radicals
  • lipid hydroperoxide
  • monoclonal antibody
  • oxidative

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    Cooke, M. S., Mistry, N., Ahmad, J., Waller, H., Langford, L., Bevan, R. J., Evans, M. D., Jones, G. D. D., Herbert, K. E., Griffiths, H. R., & Lunec, J. (2003). Deoxycytidine glyoxal: Lesion induction and evidence of repair following vitamin C supplementation in vivo. Free Radical Biology and Medicine, 34(2), 218-225. https://doi.org/10.1016/S0891-5849(02)01240-6