The metabolism of 4,8-DiMeIQx in conventional and germ-free rats

Mark G. Knize, Eva övervik, Tore Midtvedt, Ken W Turteltaub, James A. Happe, Jan Åke Gustafsson, James S. Felton

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The aromatic amine mutagen, [l4C]2-amino-3,4-8-trimethyl-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), which is derived from cooked food, was administered to conventional and germ-free AGUS rats previously fed either a semi-synthetic diet containing the cytochrome P-450 inducer β-naphtho-flavone (BNF) or a control diet without BNF. The germ-free animals had longer fecal transit times and lower induction of 7-ethoxyresorufin-O-deethylase activity than conventional rats. Induction with BNF caused a greater percentage of the radioactivity to be excreted in the feces of both germ-free and conventional rats. Feeding BNF also caused a 4-fold induction in germ-free and a 24-fold induction in conventional rat intestinal enzyme levels. Analysis of the urinary and fecal metabolites showed no consistent differences between conventional and germ-free rats in the metabolite profile. Major metabolites were identified as 8-hydroxymethyl-DiMeIQx, N-acetyl-8-hydroxymethyl-DiMelQx, and 3-N-dimethyl-4-hydroxy-methyl-DiMelQx. The data from this study indicate that intestinal microflora do not play a major role in the metabolism of 4,8-DiMeIQx, but the induction of intestinal enzymes does affect the route and rate of excretion.

Original languageEnglish (US)
Pages (from-to)1479-1484
Number of pages6
JournalCarcinogenesis
Volume10
Issue number8
DOIs
StatePublished - Aug 1989
Externally publishedYes

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience
  • Cancer Research

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