Effects of dietary and intraperitoneally administered beta-naphthoflavone on mutagenicity and tissue distribution of Trp-P-1 in the rat.
The effect of dietary beta-naphthoflavone (BNF) on tissue retention of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was studied in the rat. Female rats, 3 weeks old, were fed a BNF-containing diet for 3 days before being dosed orally or i.v. with 14C-labelled Trp-P-1. The rats were killed at 4, 24 or 48 h after dosage and subjected to tape-section autoradiography. The tissue localization of Trp-P-1-derived radioactivity was compared to that observed in untreated rats and in rats given BNF i.p. Ethoxyresorufin-O-deethylase (EROD) activity and mutagenicity of Trp-P-1 in the Ames test, using S9 prepared from forestomach, glandular stomach, small intestine, liver and lung, were used as in vitro assays to measure the degree of cytochrome P450IA1 and/or P450IA2 induction. Dietary BNF treatment caused a 30- to 40-fold increase in EROD activity in the small intestine, but only a 2-fold increase in the liver and the lung. These inter-organ differences were not observed after i.p. administration of BNF. The increase in mutagenicity of Trp-P-1 in the Ames test could be correlated to the increase in EROD activity. The autoradiographic data showed that the route of administration of BNF as well as of Trp-P-1 were important for the tissue localization of Trp-P-1. Dietary BNF treatment caused a pronounced retention of Trp-P-1-derived radioactivity in the epithelia of the small intestine, forestomach, oesophagus and the oral cavity, regardless of the administration route of Trp-P-1; a similar though less pronounced epithelial retention was observed after i.p. injection of BNF. A clear-cut boundary of accumulated radioactivity between the forestomach and the glandular stomach where the levels were almost non-detectable was observed in rats fed the BNF-containing diet. It is concluded that dietary inducers may be important determinants of metabolism and tissue distribution of toxic compounds.
Department of Medical Nutrition, Huddinge University Hospital, Sweden.
P
P
Lindeskog
I
I
Brandt
T
T
Hansson
B O
BO
Lund
J A
JA
Gustafsson
D000818:Animals; D001345:Autoradiography; D001571:Benzoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D004032:Diet; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D014018:Tissue Distribution; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002243:Carbolines; D002250:Carbon Radioisotopes; D005419:Flavonoids; D009153:Mutagens; D019324:beta-Naphthoflavone; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole