Tissue localization of the carcinogenic glutamic acid pyrolysis product Glu-P-1 in control and beta-naphthoflavone-treated mice and rats.
Autoradiograms obtained after i.v. injection of the 14C-labelled carcinogenic glutamic acid pyrolysis product Glu-P-1 to mice and rats showed a pronounced uptake of radioactivity in the liver, kidney, thyroid and nasal mucosa. High concentrations of radioactivity were present in the bile and intestinal contents at short post-injection times. In the male rat, the Zymbal's gland and the preputial gland were identified as sites of high and specific binding at all post-injection times examined. The liver and nasal mucosa were identified as sites of retention of non-extractable radioactivity. In the pigmented mouse, Glu-P-1 and/or its metabolites were accumulated in melanin. Glu-P-1 is known to be activated by cytochrome P-448. Pretreatment with beta-naphthoflavone (a cytochrome P-448 inducer) did not change the tissue localization of radioactivity in either species except for the liver where the overall labelling was decreased. Neither did pretreatment of mice with the glutathione-depleting agent phorone change the distribution pattern significantly. However, combined pretreatments of mice with either phorone or beta-naphthoflavone and the cytochrome P-448 inhibitor 9-hydroxyellipticine resulted in an increased overall retention of radioactivity in the body.
Brandt
I
I
Department of Pharmacology and Toxicology, SLU, Uppsala Biomedical Center, Sweden.
Kowalski
B
B
Gustafsson
J A
JA
Rafter
J
J
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001571:Benzoflavones / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014018:Tissue Distribution; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002250:Carbon Radioisotopes; D005419:Flavonoids; D007093:Imidazoles; D009153:Mutagens; D019324:beta-Naphthoflavone; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole