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DNA Damage by Benzo(a)pyrene in Human Cells Is Increased by Cigarette Smoke and Decreased by a Filter Containing Rosemary Extract, Which Lowers Free Radicals

Université des Sciences et Technologies de Lille, Lille 1, UMR Centre National de la Recherche Scientifique 8009, Chimie Organique et Macromoléculaire and IFR 118, Protéomique, Modifications Post-trductionnelles et Glycobiologie, Villeneuve d'Ascq, France

Requests for reprints: Kroum Alexandrov, Université des Sciences et Technologies de Lille, Lille 1, UMR Centre National de la Recherche Scientifique 8009, Chimie Organique et Macromoléculaire, 59655 Villeneuve d'Ascq Cedex, France. Phone: 33-1-60-10-44-97; Fax: 33-3-20-33-61-36; E-mail: kroum_alexandrov{at}yahoo.com.

We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide-N²-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells. This adduct is now considered to be critical event in tumorigenesis by BP. In this study, we investigate the contribution of cigarette smoke on the BPDE-dG formation. In a cell-free system, the amount of (–)-anti-BPDE-dG adduct increased linearly with concentration of cigarette smoke in the presence of (+)-BP-7,8-diol. Catalase and superoxide dismutase inhibited its formation by >80%. When MCF-7 cells were treated for 2 hours with the (+)-BP-7,8-diol, cigarette smoke increased dose dependently the formation of (–)-anti-BPDE-dG and decreased the cytochrome P450 (CYP)–dependent formation of (+)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydro-BP the adduct. Then, cells were treated for up to 1 day with BP and then exposed for 2 hours with cigarette smoke. During these 2 hours, there are twice the increase in the adduct formation in cells treated with cigarette smoke compared with levels in nontreated cells due to CYP activity. Thus, cigarette smoke containing reactive oxygen species may activate the second step of BP metabolic way, leading to the formation of BPDE-dG adduct. Cigarette smoke thus seems may be in part responsible for the formation of the critical lung tumorigenic adduct. Finally, modified cigarette filter containing rosemary extract decreases by >70% of the BPDE-dG adducts level due to the cigarette smoke in MCF-7 cells. This approach may lead to decreasing lung cancer risk in addicted smokers. (Cancer Res 2006; 66(24): 11938-45)