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

Autor: Margarita Rojas, Soisungwan Satarug, Kroum Alexandrov
Rok vydání: 2010
Předmět:
Zdroj: Toxicology Letters. 198:63-68
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2010.04.009
Popis: 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.
Databáze: OpenAIRE
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