Transfer of the food mutagen PhIP to foetuses and newborn mice following maternal exposure.
The food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is a liver carcinogen in neonatal mice. In this study the transfer of PhIP to foetuses and neonates following a single ip dose (4.7-5.2 mg/kg body weight) to pregnant or lactating C57Bl/6 mice was studied by tissue extraction and HPLC analysis. A transplacental transfer of unchanged [3H]PhIP to foetuses was demonstrated; the highest foetal levels were observed at late gestation. Autoradiography of mice injected iv with [2-14C]PhIP (1.4 mg/kg) during late gestation showed a high and selective localization of radioactivity in the pigmented parts of the foetal eye and a moderate level of radioactivity in the foetal liver, gastro-intestinal contents, urine and in the uterine fluid. HPLC analysis of stomach contents and tissues of newborn mice exposed for 4 hr to lactating dams dosed ip with [3H]PhIP (5.2 mg/kg) showed the presence of unchanged PhIP suggesting excretion of PhIP in the milk of the dams. The results in this study raise concern that exposure to PhIP during pregnancy and nursing may result in a transfer of this food mutagen to foetuses and infants.
Brittebo
E B
EB
Department of Pharmacology, University of Lund, Sweden.
Karlsson
A A
AA
Skog
K I
KI
Jägerstad
I M
IM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001345:Autoradiography; D002273:Carcinogens / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007093:Imidazoles / Q000032:analysis / Q000493:pharmacokinetics*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000493:pharmacokinetics*; D011247:Pregnancy; D014018:Tissue Distribution
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine