Can vitamin C induce nucleotide excision repair? Support from in vitro evidence.
Intracellular vitamin C acts to protect cells against oxidative stress by intercepting reactive oxygen species (ROS) and minimising DNA damage. However, rapid increases in intracellular vitamin C may induce ROS with subsequent DNA damage priming DNA repair processes. Herein, we examine the potential of vitamin C and the derivative ascorbate-2-phosphate (2-AP) to induce a nucleotide excision repair (NER) response to DNA damage in a model of peripheral blood mononuclear cells. Exposure of cells to elevated levels of vitamin C induced ROS activity, resulting in increased levels of deoxycytidine glyoxal (gdC) and 8-oxo-2'-deoxyguanosine (8-oxodG) adducts in DNA; a stress response was also induced by 2-AP, but was delayed in comparison to vitamin C. Evidence of gdC repair was also apparent. Measurement of cyclobutane thymine-thymine dimers (T < >T) in DNA and culture supernatant were included as a positive marker for NER activity; this was evidenced by a reduction in DNA and increases in culture supernatant levels of T < >T for vitamin C-treated cells. Genomics analysis fully supported these findings confirming that 2-AP, in particular, induced genes associated with stress response, cell cycle arrest, DNA repair and apoptosis, and additionally provided evidence for the involvement of vitamin C in the mobilisation of intracellular catalytic Fe.
Bevan
Ruth J
RJ
Institute of Environment and Health, Cranfield Health, Cranfield University, Cranfield, Bedfordshire, MK43 0AL, UK. r.bevan@cranfield.ac.uk
Mistry
Nalini
N
Patel
Parul R
PR
Halligan
Eugene P
EP
Dove
Rosamund
R
Lunec
Joseph
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005819:Genetic Markers; D023281:Genomics; D006037:Glyoxal / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008954:Models, Biological; D011740:Pyrimidine Dimers / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology*
D005819:Genetic Markers; D011740:Pyrimidine Dimers; D017382:Reactive Oxygen Species; D014815:Vitamins; C011669:ascorbate-2-phosphate; D006037:Glyoxal; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D007501:Iron; D003849:Deoxyguanosine; D001205:Ascorbic Acid