The metabolism of 2,5-diphenyloxazole (PPO) in human lymphocytes and rat liver microsomes

  • Pharmacol Toxicol. 1987 Sep;61(3):184-90. doi: 10.1111/j.1600-0773.1987.tb01800.x.
J T Ahokas  1 ,  C Davies ,  N Jacobsen ,  N T Kärki ,  A Philippides ,  A M Treston
Affiliations
  • 1. Department of Applied Biology, Royal Melbourne Institute of Technology, Vic, Australia.
PMID: 3684951 DOI: 10.1111/j.1600-0773.1987.tb01800.x
Abstract

The oxidative metabolism of 2,5-diphenyloxazole (PPO) is associated with 3-methylcholanthrene inducible cytochrome P-450. The major metabolite formed has m/z of 237, corresponding to hydroxylated PPO. All the possible hydroxylated metabolites of PPO were synthesized and characterized, enabling the assignment of a structure for the major metabolite and two minor metabolites. The metabolites are easily extracted and their fluorescence is quantifiable in alkaline medium with a sample fluorescence to blank fluorescence ratio of 400:1. A sensitive HPLC assay of PPO metabolism was also developed. PPO metabolism is readily catalyzed by 3-methylcholanthrene-induced rat liver microsomes and strongly inhibited by alpha-naphthoflavone, but poorly inhibited by metyrapone or SKF 525A, indicating the involvement of cytochrome P-448 or P1-450 in the metabolism of PPO. With human lymphocytes the method has proven to be a good indicator of "aryl hydrocarbon hydroxylase" (AHH) activity, correlating well with AHH assays using benzo(alpha)pyrene (BP) as a substrate. Both the induced BP and PPO metabolism by human lymphocytes is inhibited by alpha-naphthoflavone, but not by metyrapone.

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