These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Regioselective and stereoselective metabolisms of pyrene and 1-bromopyrene by rat liver microsomes and effects of enzyme inducers.
    Author: Shou M, Yang SK.
    Journal: Drug Metab Dispos; 1988; 16(2):173-83. PubMed ID: 2898329.
    Abstract:
    Due to the symmetrical property of pyrene (Py), trans-dihydrodiols formed at 4,5- and 9,10-positions are identical, as are the monohydroxylated products (phenols) formed at C1, C3, C6, and C8 positions. With a bromo substituent at C1 position of Py, 1-bromopyrene (1-BrPy) trans-4,5-dihydrodiol and 1-BrPy trans-9,10-dihydrodiol are distinctly different products, as are the phenolic products formed at C3, C6, and C8 positions. Products formed in the oxidative metabolism of 1-BrPy by rat liver microsomes were characterized by retention times on reversed-phase high performance liquid chromatography (HPLC), and by ultraviolet-visible absorption and mass spectral analyses. We have compared regioselective and stereoselective metabolisms at the K- and non-K-regions of Py and 1-BrPy by liver microsomes from untreated (control), phenobarbital (PB)-treated, 3-methylcholanthrene (MC)-treated, and polychlorinated biphenyls (PCB, Aroclor 1254)-treated rats. The effects of inducers on the relative amounts of non-K-region phenols formed in the metabolisms of Py and 1-BrPy by rat liver microsomes were: MC greater than PCB greater than PB greater than control. The relative order was PB greater than PCB greater than MC greater than control for the formation of both 1-BrPy trans-4,5-dihydrodiol and 1-BrPy trans-9,10-dihydrodiol in the metabolism of 1-BrPy. The ratios between metabolically formed 1-BrPy trans-4,5-dihydrodiol to Py trans-4,5-dihydrodiol, using 0.5 mg of microsomal protein per ml of incubation mixture, were between 0.4 and 0.6 in the presence of liver microsomes from untreated, PB-treated, and PCB-treated rats. However, the ratio was approximately 1.5 using liver microsomes from MC-treated rats. The ratios between the sum of 1-BrPy trans-9,10-dihydrodiol and 1-BrPy 9,10-epoxide to Py trans-9,10-dihydrodiol, and to 1-BrPy trans-4,5-dihydrodiol were in the range of 0.1 to 0.5 using four rat liver microsomal preparations. These data revealed the effects of a bromo substituent at C1 of Py on the regioselectivity of various rat liver microsomal enzymes toward the oxidative metabolism at various positions of 1-BrPy. The enantiomeric compositions of K-region dihydrodiols formed by four rat liver microsomal preparations were determined by chiral stationary phase HPLC and circular dichroism spectral analyses; the percentage of R,R-enantiomers were: Py trans-4,5-dihydrodiol, 78-79%; 1-BrPy trans-4,5-dihydrodiol, 74-77%; 1-BrPy trans-9,10-dihydrodiol, 86-97%.
    [Abstract] [Full Text] [Related] [New Search]