TY - JOUR
T1 - The metabolism of 4,8-DiMeIQx in conventional and germ-free rats
AU - Knize, Mark G.
AU - övervik, Eva
AU - Midtvedt, Tore
AU - Turteltaub, Kenneth W.
AU - Happe, James A.
AU - Gustafsson, Jan-Ake
AU - Felton, James S.
PY - 1989/8/1
Y1 - 1989/8/1
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/10.8.1479
DO - 10.1093/carcin/10.8.1479
M3 - Article
C2 - 2665968
AN - SCOPUS:0024318799
VL - 10
SP - 1479
EP - 1484
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 8
ER -