In vitro investigations into the interaction of beta-carotene with DNA: evidence for the role of carbon-centered free radicals.
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.
Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. j.kleinjans@grat.unimaas.nl
Jos C S
JC
Kleinjans
Marcel H M
MH
van Herwijnen
Jan M S
JM
van Maanen
Lou M
LM
Maas
Theo M C M
TM
de Kok
Harald J J
HJ
Moonen
Jacob J
JJ
Briedé
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002244:Carbon / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D017382:Reactive Oxygen Species / Q000378:metabolism; D012474:Salmon / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism*
D018736:DNA Adducts; D005609:Free Radicals; D017382:Reactive Oxygen Species; D019207:beta Carotene; D002244:Carbon; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine