The metabolism of 4,8-DiMeIQx in conventional and germ-free rats.
The aromatic amine mutagen, [14C]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 beta-naphthoflavone (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-DiMeIQx, and 3-N-dimethyl-4-hydroxy-methyl-DiMeIQx. 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 not affect the route and rate of excretion.
Knize
M G
MG
Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Overik
E
E
Midtvedt
T
T
Turteltaub
K W
KW
Happe
J A
JA
Gustafsson
J A
JA
Felton
J S
JS
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005856:Germ-Free Life; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D011810:Quinoxalines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D002250:Carbon Radioisotopes; D009153:Mutagens; D011810:Quinoxalines; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine