Incorporation of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) into fur and correlation with intestinal tumourigenesis in Min/+ mice.
The purpose of this work was to correlate the amount of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) determined in mouse fur with the number of intestinal tumours induced by PhIP, to further evaluate incorporation of PhIP into hair as a putative exposure biomarker for food mutagens. We have previously shown that PhIP increases intestinal tumourigenesis in C57BL/6J-Min/+ (Multiple Intestinal Neoplasia) mice. Fur was sampled from mice exposed according to various PhIP protocols, and the amount of PhIP in the fur was quantitated by high performance liquid chromatography - mass spectrometry (HPLC-MS). A quantitative incorporation of PhIP in the fur was demonstrated after a single subcutaneous injection of PhIP, and between one and eight PhIP exposures either via direct subcutaneous injections or through breast milk from PhIP-injected dams. However, after higher exposures, the amount of PhIP in the fur appeared to reach saturation. After low exposures to PhIP, the number of intestinal tumours correlated with the amount of PhIP in the fur of individual mice, whereas after higher exposures, the number of tumours was relatively higher than the amounts of incorporated PhIP in the fur. Other factors, e.g. amounts of reactive PhIP metabolites formed, are also determining the number of intestinal tumours. The demonstrated quantitative incorporation of PhIP into mice fur and the correlation with number of intestinal tumours at the lower exposures, indicate that determination of PhIP in human hair may be a suitable biomarker for exposure to dietary PhIP, which is found in human hair in 10-3 lower amounts than in these mice.
Steffensen
Inger-Lise
IL
Department of Food Toxicology, Norwegian Institute of Public Health, Oslo, Norway. inger-lise.steffensen@fhi.no
Janak
Karel
K
Hegstad
Solfrid
S
Andreassen
Ashild
A
Paulsen
Jan Erik
JE
Reistad
Ragnhild
R
Alexander
Jan
J
D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005502:Food; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism / Q000633:toxicity*; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine