Carcinogenesis Advance Access originally published online on December 4, 2008
Carcinogenesis 2009 30(2):308-314; doi:10.1093/carcin/bgn270
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The carotenoid β-cryptoxanthin stimulates the repair of DNA oxidation damage in addition to acting as an antioxidant in human cells
1 Department of Nutrition, Faculty of Medicine, University of Oslo, PO Box 1046 Blindern, 0316 Oslo, Norway
2 Department of Medical Oncology, Hospital Universitario Puerta de Hierro, 28035 Madrid, Spain
3 Department of Molecular Biology, Centre for Molecular Biology and Neuroscience, Institute of Microbiology, Rikshospitalet Medical Centre, 0027 Oslo, Norway
* To whom correspondence should be addressed. Tel: +47 22851360; Fax: +47 22851341; Email: a.r.collins{at}medisin.uio.no
The role of dietary antioxidants in human health remains controversial. Fruits and vegetables in the diet are associated with lower rates of chronic disease, and this is often attributed to their content of antioxidants, and a resulting protection against oxidative stress. However, large-scale human trials with antioxidant supplements have shown, if anything, an increase in mortality. We have investigated the biological properties of β-cryptoxanthin, a common carotenoid, in cell culture model systems, using the comet assay to measure DNA damage. At low concentrations, close to those found in plasma, β-cryptoxanthin does not itself cause damage, but protects transformed human cells (HeLa and Caco-2) from damage induced by H2O2 or by visible light in the presence of a photosensitizer. In addition, it has a striking effect on DNA repair, measured in different ways. Incubation of H2O2-treated cells with β-cryptoxanthin led to a doubling of the rate of rejoining of strand breaks and had a similar effect on the rate of removal of oxidized purines by base excision repair. The latter effect was confirmed with an in vitro assay: cells were incubated with or without β-cryptoxanthin before preparing an extract, which was then incubated with substrate DNA containing 8-oxo-7,8-dihydroguanine; incision was more rapid with the extract prepared from carotenoid-preincubated cells. No significant increases were seen in protein content of human 8-oxoguanine DNA glycosylase 1 or apurinic endonuclease 1. The apparent cancer-preventive effects of dietary carotenoids may depend on the enhancement of DNA repair as well as antioxidant protection against damage.
Abbreviations: APE1, apurinic endonuclease 1; BER, base excision repair; DMSO, dimethyl sulphoxide; FPG, formamidopyrimidine DNA glycosylase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HEPES, N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid; OGG1, 8-oxoguanine DNA glycosylase 1; 8-oxoGua, 8-oxo-7,8-dihydroguanine; PBS, phosphate-buffered saline; SB, strand break
Received June 23, 2008; revised November 20, 2008; accepted November 20, 2008.
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