Cytochrome P450IIE1 Metabolism of Pyridines: Evidence for Production of a Reactive Intermediate which Exhibits Redox-Cycling Activity and Causes DNA Damage
To date some thirty pyridine derivatives have been identified as being present in cigarette smoke and smoke condensate as revealed by chromatographic analysis of smoke composition (Schumacher, et al., 1977; Moree-Testa, et al.; 1984). 3-Hydroxypyridine has been shown to be present in tobacco smoke and its content was estimated to be as high as 0.13 mg per cigar smoked (Schmelt and Stedman, 1962; Osman et al., 1963). Although studies on the metabolism of 3- and 2-hydroxypyridine in microorganisms have been reported (Houghton and Cain, 1972), information concerning the cytochrome P-450-dependent metabolism of these agents or the specificity of individual forms of P-450 for these substrates is lacking.
KeywordsPyridine Derivative NADPH Oxidation Microsomal Suspension Single Strand Breakage Open Circular Form
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