Carcinogenesis Advance Access published online on February 26, 2004
Carcinogenesis, doi:10.1093/carcin/bgh125
© 2004 by Oxford University Press
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CARCINOGENESIS
1 Department of Health Risk Analysis & Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
* Corresponding author. E-mail: j.kleinjans{at}grat.unimaas.nl.
Received 8 September 2003
; revised 12 February 2004
; accepted 14 February 2004
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In vitro investigations into the interaction of beta-carotene with DNA: evidence for the role of carbon-centered free radicals
-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 -carotene, prooxidant characteristics of -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 -carotene; furthermore, -carotene oxidation products may have a role in the bioactivation of B[a]P analogous to the peroxide-shunt pathway of cytochrome P-450 supported by cumene hydroperoxide. The aim of this study was to assess the effects of -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 -carotene in the presence of various metabolizing systems was not able to induce oxidative DNA damage (8-oxo-dG), although -carotene is capable of generating ROS spontaneously in the absence of metabolizing fractions. Also, we could not find an effect of -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 -carotene radical which was found to be able to interact with B[a]P, and to intercalate with DNA.
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