Journal Article

Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung

Yvonne G.J. van Helden, Jaap Keijer, Sandra G. Heil, Catalina Picó, Andreu Palou, Paula Oliver, Armelle Munnia, Jacob J. Briedé, Marco Peluso, Nicole L. Franssen-van Hal, Frederik J. van Schooten and Roger W. L. Godschalk

in Carcinogenesis

Volume 30, issue 12, pages 2070-2076
Published in print December 2009 | ISSN: 0143-3334
Published online July 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp186
Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung

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Beta-carotene (BC) was found to enhance lung cancer risk in smokers. This adverse effect was unexpected because BC was thought to act as an anti-oxidant against cigarette smoke-derived radicals. These radicals can directly or indirectly damage DNA, leading to the formation of pro-mutagenic DNA lesions such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG). Later, it was suggested that high concentrations of BC could also result in pro-oxidant effects. Therefore, we investigated whether high but physiologically feasible concentrations of BC were able to alter (i) the formation of radicals in vitro assessed by electron spin resonance spectroscopy, (ii) the levels of 8-oxo-dG and M1dG in vitro in lung epithelial cells after incubation with hydrogen peroxide (H2O2) and the smoke-derived carcinogen benzo[a]pyrene (B[a]P) and (iii) the levels of 8-oxo-dG and M1dG in vivo in ferrets’ lung after chronic exposure to B[a]P. BC increased in vitro hydroxyl radical formation in the Fenton reaction but inhibited the formation of carbon-centered radicals. Similarly, BC was able to enhance 8-oxo-dG in vitro in lung epithelial cells. On the other hand, BC significantly inhibited M1dG formation in lung epithelial cells, especially after induction of M1dG by H2O2 or B[a]P. Finally, BC supplementation of ferrets also resulted in a significant decrease in M1dG, but in contrast to the in vitro experiments, no effect was observed on 8-oxo-dG levels, probably because of increased base excision repair capacities as assessed by a modified comet assay. These data indicate that the fate of BC being a pro- or anti-oxidant strongly depends on the type of radical involved.

Journal Article.  6089 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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