The effects of cytochrome P-450-448 inhibitors on the binding of benzo(a)pyrene and derivatives to DNA upon microsomal activation

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
W I Liu, N H Sloane

Abstract

1. [3H]Benzo(a)pyrene and 6-substituted derivatives of [3H]benzo(a)pyrene are covalently bound to calf thymus DNA upon reaction with microsomal preparations from rats pretreated with 3-methylcholanthrene in the presence of NADPH. Two different types of cytochrome P-450-448 inhibitors, alpha-naphthoflavone and 1-benzylimidazole, show greater than 80% inhibition of the binding of benzo(a)pyrene to DNA. 2. In the presence of these inhibitors, 6-hydroxymethylbenzo(a)pyrene, 6-methylbenzo(a)pyrene and 6-formylbenzo(a)pyrene show varying degrees of inhibition of binding to DNA depending upon the inhibitor employed. 3. Polyguanylic acid is the most effective substrate for the binding of each activated polynuclear aromatic hydrocarbon; polyadenylic acid and DNA show essentially equivalent binding.

Citations

Apr 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·T MeehanM Calvin
May 1, 1977·Archives of Biochemistry and Biophysics·E BresnickH Mukhtar
Oct 15, 1975·International Journal of Cancer. Journal International Du Cancer·M R OsborneP BROOKES
Apr 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·N Kinoshita, H V Gelboin
Dec 1, 1972·British Journal of Cancer·F DewhurstG Calcutt
Mar 15, 1973·International Journal of Cancer. Journal International Du Cancer·J W Flesher, K L Sydnor
Oct 15, 1971·FEBS Letters·P L. GroverP Sims

Related Concepts

20-Methylcholanthrene
Derivatives
Poly G
Lung
Adenine Polynucleotides
Polycyclic Hydrocarbons, Aromatic
Microsomes
Cytochrome P450
Pyrene
Calf thymus DNA

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