ABSTRACT
To survive and thrive in the chemical environment in which it exists, the living organism has developed a number of versatile enzyme systems that facilitate the complete elimination of xenobiotics to which it is inescapably exposed by converting them metabolically to hydrophilic, readily excretable, metabolites. Cytochromes P450, a superfamily of enzymes, are undoubtedly the most prolific enzyme system in xenobiotic metabolism, capable of catalyzing efficiently the metabolism of structurally very diverse compounds. Paradoxically, however, such metabolism may also lead to the generation of reactive intermediates that interact covalently with cellular macromolecules, giving rise to various forms of toxicity, including carcinogenicity, a process referred to as bioactivation. As a defense mechanism, the body can deactivate
Abstract .................................................................................................................. 253 Introduction ............................................................................................................254 Metabolism of Xenobiotics ....................................................................................254 Cytochromes P450 in the Metabolism of Xenobiotics ..........................................256 Biochemical Activation of Chemicals ................................................................... 257 Balance of activation and deactivation .................................................................. 259 Bioactivation of Chemical Carcinogens ................................................................ 261 Role of Cytochrome P450 Proteins in the Bioactivation of Chemical
Carcinogens ................................................................................................. 262 Regioselectivity in the Metabolism of Chemical Carcinogens
by Cytochrome P450 ...................................................................................264 Cytochrome P450 Induction and Chemical Carcinogenesis .................................266 References ..............................................................................................................268
