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The Role of Cytochrome P450 Enzymes in Carcinogen Metabolism: Lessons Learned From Studies With Benzo[a]pyrene and Aristolochic Acid

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10391194" target="_blank" >RIV/00216208:11310/18:10391194 - isvavai.cz</a>

  • Výsledek na webu

    <a href="http://dx.doi.org/10.1142/9789813237209_0002" target="_blank" >http://dx.doi.org/10.1142/9789813237209_0002</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1142/9789813237209_0002" target="_blank" >10.1142/9789813237209_0002</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    The Role of Cytochrome P450 Enzymes in Carcinogen Metabolism: Lessons Learned From Studies With Benzo[a]pyrene and Aristolochic Acid

  • Popis výsledku v původním jazyce

    This chapter summarizes the latest data increasing our knowledge on a function of cytochrome P450 (P450) enzymes in metabolism of several carcinogens and on the mechanisms of the reaction cycle catalyzed by the P450-monooxygenase system. Particularly it describes the P450-dependent metabolism, toxicity, and carcinogenicity of two human environmental carcinogens, benzo[a]pyrene (BP) and aristolochic acid I (AAI). This chapter focuses on studies that have specifically investigated the role of P450 enzymes in the bioactivation and detoxification of BP and AAI, and the lessons learned from these studies in examining the potential role of P450-mediated metabolism for other known or putative human environmental carcinogens. P450 enzymes play a key role both in metabolic activation of these human carcinogens to the reactive intermediates forming DNA adducts, and in their detoxification to metabolites that are excreted. While BaP is oxidatively metabolized (activated or detoxified) by P450s, AAI can be metabolized both oxidatively (to its detoxification metabolite aristolochic acid Ia [AAIa]) and reductively (to be activated to DNA-binding metabolites). Concerning the mechanisms of reactions catalyzed by the microsomal P450 monooxygenase system reviewed in this chapter, it is demonstrated that besides NADPH:cytochrome P450 oxidoreductase (POR), the system consisting of microsomal NADPH:cytochrome b5 reductase together with its substrate cytochrome b5 and cofactor NADH can function as a donor of electrons both for the first and the second reduction of at least some of P450 enzymes in their reaction cycle. These findings indicate that the old myth, the generally accepted mechanism on the exclusivity of the POR/NADPH system for reduction of several P450s, should be revised.

  • Název v anglickém jazyce

    The Role of Cytochrome P450 Enzymes in Carcinogen Metabolism: Lessons Learned From Studies With Benzo[a]pyrene and Aristolochic Acid

  • Popis výsledku anglicky

    This chapter summarizes the latest data increasing our knowledge on a function of cytochrome P450 (P450) enzymes in metabolism of several carcinogens and on the mechanisms of the reaction cycle catalyzed by the P450-monooxygenase system. Particularly it describes the P450-dependent metabolism, toxicity, and carcinogenicity of two human environmental carcinogens, benzo[a]pyrene (BP) and aristolochic acid I (AAI). This chapter focuses on studies that have specifically investigated the role of P450 enzymes in the bioactivation and detoxification of BP and AAI, and the lessons learned from these studies in examining the potential role of P450-mediated metabolism for other known or putative human environmental carcinogens. P450 enzymes play a key role both in metabolic activation of these human carcinogens to the reactive intermediates forming DNA adducts, and in their detoxification to metabolites that are excreted. While BaP is oxidatively metabolized (activated or detoxified) by P450s, AAI can be metabolized both oxidatively (to its detoxification metabolite aristolochic acid Ia [AAIa]) and reductively (to be activated to DNA-binding metabolites). Concerning the mechanisms of reactions catalyzed by the microsomal P450 monooxygenase system reviewed in this chapter, it is demonstrated that besides NADPH:cytochrome P450 oxidoreductase (POR), the system consisting of microsomal NADPH:cytochrome b5 reductase together with its substrate cytochrome b5 and cofactor NADH can function as a donor of electrons both for the first and the second reduction of at least some of P450 enzymes in their reaction cycle. These findings indicate that the old myth, the generally accepted mechanism on the exclusivity of the POR/NADPH system for reduction of several P450s, should be revised.

Klasifikace

  • Druh

    C - Kapitola v odborné knize

  • CEP obor

  • OECD FORD obor

    10608 - Biochemistry and molecular biology

Návaznosti výsledku

  • Projekt

  • Návaznosti

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Ostatní

  • Rok uplatnění

    2018

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název knihy nebo sborníku

    Carcinogens, DNA Damage and Cancer Risk: Mechanisms of Chemical Carcinogenesis

  • ISBN

    978-981-323-721-6

  • Počet stran výsledku

    48

  • Strana od-do

    21-68

  • Počet stran knihy

    374

  • Název nakladatele

    World Scientific Publishing Co. Pte. Ltd.

  • Místo vydání

    Singapur

  • Kód UT WoS kapitoly