Carcinogenesis, Vol 18, 1049-1054, Copyright © 1997 by Oxford University Press
IL Steffensen, JE Paulsen, TJ Eide and J Alexander
The multiple intestinal neoplasia (Min) mice have a mutation in the murine
adenomatous polyposis coli (Apc) gene rendering them highly susceptible to
spontaneous intestinal adenoma formation, similar to the familial
adenomatous polyposis (FAP) syndrome in humans. We studied whether the most
abundant mutagenic heterocyclic amine isolated from cooked food,
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), could influence
early intestinal neoplasia in C57BL/6J-Min/+ and C57BL/6J- +/+ (wild-type)
mice of both sexes. PhIP was given in 4 weekly i.p. injections of 50 mg/kg.
Ten weeks after the start of the experiment, PhIP had significantly
increased the numbers of small tumors and cystic crypts in the proximal
section of the small intestine in male Min/+ mice, and the numbers of
aberrant crypt foci (ACF) in the large intestines of both males and
females. The effects of PhIP were more pronounced in male than in female
Min/+ mice. In +/+ mice, no tumors or cystic crypts in the small intestine,
and no tumors and only a very few ACF in the large intestine, were induced
by PhIP. These results show that a substance frequently present in the
human diet is able to enhance the neoplastic process induced by a genetic
lesion, which is also commonly found both in inherited and sporadic colon
carcinomas in humans.
ARTICLES
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine increases the numbers of tumors, cystic crypts and aberrant crypt foci in multiple intestinal neoplasia mice
National Institute of Public Health, Department of Environmental Medicine, Torshov, Oslo, Norway.
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