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

Abstract:

: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Kleinjans JC,van Herwijnen MH,van Maanen JM,Maas LM,de Kok TM,Moonen HJ,Briedé JJ

doi

10.1093/carcin/bgh125

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

1249-56

issue

7

eissn

0143-3334

issn

1460-2180

pii

bgh125

journal_volume

25

pub_type

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