Binding of the food mutagen PhIP in pigmented tissues of mice.
The distribution of the 14C-labelled food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the tissues of C57B1/6 and NMRI mice was studied. The results showed a high and selective binding of radioactivity in the pigment epithelium of the eye and in the fur following a single dose (0.3-4 mg/kg) of [14C]PhIP in the pigmented C57B1/6 mice whereas no such localization of radioactivity was present in the albino NMRI mice. A low but selective covalent binding of radioactivity was observed in the liver, inner cortex of the kidney and in the tracheal mucosa of [14C]PhIP-injected mice. PhIP was firmly bound to synthetic melanin pigment in vitro; only 3% was released by extraction with a phosphate buffer (pH 7) whereas 72% was released by extraction by methanol:conc. NH3 (15:1). Three hours to 7 days following a single injection of [14C]PhIP in C57B1/6 mice the radioactivity in the eye was 3- to 6-fold higher than that in the liver or kidney. Almost 60% of the radioactive material present in the pigmented epithelium of the eye 3 and 24 h following injection could be extracted by basic methanol and identified as unchanged PhIP. The residual radioactivity in the pigmented epithelium of the eyes may represent a covalent binding of [14C]PhIP metabolites to cellular constituents or to a basic methanol-resistant binding of [14C]PhIP to melanin. The results indicate that pigmented tissues may be potential target tissues for the toxic effects of PhIP and suggest that the use of hair for biological monitoring of PhIP should be examined.
Brittebo
E B
EB
Department of Pharmacology, University of Lund, Sweden.
Skog
K I
KI
Jägerstad
I M
IM
D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005502:Food; D006197:Hair / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism* / Q000493:pharmacokinetics; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000378:metabolism* / Q000493:pharmacokinetics; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011874:Radiometry; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
D007093:Imidazoles; D008543:Melanins; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine