title: The critical DNA damage by benzo(a)pyrene in lung tissues of smokers and approaches to preventing its formation.
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.
authors.affiliation: Centre National de la Recherché Scientifique, Paris, France. kroum_alexandrov@yahoo.com
authors.forename: Kroum
authors.initials: K
authors.lastname: Alexandrov
authors.forename: Margarita
authors.initials: M
authors.lastname: Rojas
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D002104:Cadmium / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D004781:Environmental Exposure / Q000706:statistics & numerical data; D005609:Free Radicals / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002274:Carcinogens, Environmental; D005609:Free Radicals; D002104:Cadmium; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System