Journal Article

<i>In vitro</i> investigations into the interaction of β-carotene with DNA: evidence for the role of carbon-centered free radicals

Jos C. S. Kleinjans, Marcel H. M. van Herwijnen, Jan M. S. van Maanen, Lou M. Maas, Theo M. C. M. de Kok, Harald J. J. Moonen and Jacob J. Briedé

in Carcinogenesis

Volume 25, issue 7, pages 1249-1256
Published in print July 2004 | ISSN: 0143-3334
Published online July 2004 | e-ISSN: 1460-2180 | DOI:
In vitro investigations into the interaction of β-carotene with DNA: evidence for the role of carbon-centered free radicals

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Supplementation by β-carotene has unexpectedly appeared to increase lung cancer risk among smokers. In order to explain this it has been suggested that at high serum levels of β-carotene, prooxidant characteristics of β-carotene may become manifest, yielding reactive oxygen species (ROS) and inducing oxidative DNA damage. It has further been hypothesized that cigarette smoke carcinogens such as benzo[a]pyrene (B[a]P) and/or B[a]P metabolites, may directly react with β-carotene. Furthermore, β-carotene oxidation products may have a role in the bioactivation of B[a]P analogous to the peroxide shunt pathway of cytochrome P450 supported by cumene hydroperoxide. The aim of this study was to assess the effects of β-carotene on the formation of B[a]P–DNA adducts and oxidative DNA damage in vitro in isolated DNA, applying as metabolizing systems rat liver and lung metabolizing fractions and lung metabolizing fractions from smoking and non-smoking humans. We established that β-carotene in the presence of various metabolizing systems was unable to induce oxidative DNA damage (8-oxo-dG), although β-carotene is capable of generating ROS spontaneously in the absence of metabolizing fractions. We also could not find an effect of β-carotene on DNA adduct formation induced by B[a]P upon metabolic activation. We could, however, provide evidence of the occurrence of a carbon-centered β-carotene radical which was found to be able to interact with B[a]P and to intercalate in DNA.

Keywords: B[a]P, benzo[a]pyrene; dG, 2′-deoxyguanosine; DMPO, 5,5-dimethyl-1-pyrroline-N-oxide; DMSO, dimethylsulfoxide; DRZ, diagonal radioactive zone; ESR, electron spin resonance; HPLC-ECD, high performance liquid chromatography with electrochemical detection; 8-oxo-dG, 7-hydroxy-8-oxo-2′-deoxyguanosine; PAHs, polycyclic aromatic hydrocarbons; PEI, polyethyleneimine; POBN, α-(4-pyridyl-1-oxide)-N-t-butylnitrone; ROS, reactive oxygen species; SOD, superoxide dismutase; THF, tetrahydrofuran

Journal Article.  6157 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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