Carcinogenesis Advance Access originally published online on February 26, 2004
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Carcinogenesis, Vol. 25, No. 7, 1249-1256,
July 2004
Carcinogenesis vol.25 no.7 © Oxford University Press 2004; all rights reserved.
ARTICLE |
In vitro investigations into the interaction of ß-carotene with DNA: evidence for the role of carbon-centered free radicals
Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
1 To whom correspondence should be addressed Email: j.kleinjans{at}grat.unimaas.nl
Supplementation by ß-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 ß-carotene, prooxidant characteristics of ß-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 ß-carotene. Furthermore, ß-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 ß-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 ß-carotene in the presence of various metabolizing systems was unable to induce oxidative DNA damage (8-oxo-dG), although ß-carotene is capable of generating ROS spontaneously in the absence of metabolizing fractions. We also could not find an effect of ß-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 ß-carotene radical which was found to be able to interact with B[a]P and to intercalate in DNA.
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