Deoxycytidine glyoxal: lesion induction and evidence of repair following vitamin C supplementation in vivo.
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.
Cooke
Marcus S
MS
Oxidative Stress Group, Department of Clinical Biochemistry, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK. msc5@le.ac.uk
Mistry
Nalini
N
Ahmad
Jabeen
J
Waller
Helen
H
Langford
Lynda
L
Bevan
Ruth J
RJ
Evans
Mark D
MD
Jones
George D D
GD
Herbert
Karl E
KE
Griffiths
Helen R
HR
Lunec
Joseph
J
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
D018736:DNA Adducts; D011740:Pyrimidine Dimers; D003841:Deoxycytidine; D008315:Malondialdehyde; D006037:Glyoxal; D001205:Ascorbic Acid