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Toxicol Lett. 2010 Sep 15;198(1):63-8. doi: 10.1016/j.toxlet.2010.04.009. Epub 2010 Apr 24.

The critical DNA damage by benzo(a)pyrene in lung tissues of smokers and approaches to preventing its formation.

Author information

1
Centre National de la Recherché Scientifique, Paris, France. kroum_alexandrov@yahoo.com

Abstract

Benzo(a)pyrene (BP) and cadmium are environmental pollutants found in foodstuffs, cigarette smoke, and polluted air. BP is converted in liver and lung to benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) by the enzymes of the cytochrome P450 (CYP) superfamily, namely CYP1A1/1A2, and CYP1B1. BPDE reacts with DNA primarily at the N(2)-position of guanine, producing benzo(a)pyrene-7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-dG) adduct. BPDE reacts with DNA also at N(6) position of adenine, producing the minor N(6)-deoxyadenosine adduct, but BPDE-dG adduct is a well-established risk factor for lung cancer. We thus argue that BPDE-dG adduct could be used as a model biomarker in searching and validating of approaches to reducing lung cancer risk. If the formation of BPDE-dG adduct were to be inhibited or blocked in bronchial epithelial cells, so could lung cancer development. The best way to lower BPDE-dG formation in the lung is to stop smoking. However, the following approaches could also be considered for highly addicted smokers: (a) decrease BP and cadmium intake from food, cigarettes and other environmental sources; (b) avoid meat and other food high in BP and cadmium; (c) decrease the CYP-mediated conversion of BP in liver and lung; (d) lower free radicals and cadmium in cigarette smoke; and (e) increase BPDE detoxification.

PMID:
20399842
DOI:
10.1016/j.toxlet.2010.04.009
[Indexed for MEDLINE]

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