In vitro investigations into the interaction of  -carotene with DNA: evidence for the role of carbon-centered free radicals

• Published in: Carcinogenesis (New York) 2004-07, Vol.25 (7), p.1249-1256
• Main Author: Kleinjans, J. C. S.
• Format: Article
• Language: English
• ISSN: 1460-2180; 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgh125

Supplementation by [beta]-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 [beta]-carotene, prooxidant characteristics of [beta]-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 [beta]-carotene. Furthermore, [beta]-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 [beta]-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 [beta]-carotene in the presence of various metabolizing systems was unable to induce oxidative DNA damage (8-oxo-dG), although [beta]-carotene is capable of generating ROS spontaneously in the absence of metabolizing fractions. We also could not find an effect of [beta]-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 [beta]-carotene radical which was found to be able to interact with B[a]P and to intercalate in DNA.