Carcinogenesis, Vol. 23, No. 8, 1373-1378,
August 2002
© 2002 Oxford University Press
CARCINOGENESIS |
The food mutagen 2-amino-9H-pyrido[2,3-b]indole (A
C) but not its methylated form (MeAC) increases intestinal tumorigenesis in neonatally exposed multiple intestinal neoplasia mice
Department of Food Toxicology, Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
The heterocyclic amines 2-amino-9H-pyrido[2,3-b]indole (A
C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAC) are carcinogenic in several organs in rodents, but not in the intestinal tract. However, AC induces DNA adducts, mutations and preneoplastic aberrant crypt foci (ACF) in rodent colons. The purpose of this study was to examine whether AC and MeAC could affect intestinal tumorigenesis in C57BL/6J-Min/+ (multiple intestinal neoplasia) mice. These mice are heterozygous for a germline nonsense mutation in codon 850 of the tumor suppressor gene adenomatous polyposis coli (Apc), producing a truncated non-functional Apc protein. They develop multiple intestinal adenomas, and are particularly susceptible to intestinal carcinogens that affect the Apc gene, especially when exposed neonatally. Whole litters consisting of Min/+ and +/+ (wild-type) mice of both sexes were given a single s.c. injection of 0.22 mmol/kg AC (40.3 mg/kg) or MeAC (43.4 mg/kg) or the vehicle 1:1 dimethylsulfoxide:0.9% NaCl on days 3–6 after birth, and were terminated at 11 weeks. AC increased the number and diameter of small intestinal tumors, but not the number of colonic tumors or dysplastic ACF, in female and male Min/+ mice separately. In pooled data from females and males, colonic tumors and ACF found after AC exposure appeared to be smaller than the spontaneous lesions, indicating later induction, slower growth or both. In contrast to AC, MeAC did not affect intestinal tumorigenesis in Min/+ mice. No effects were found by any of the amino--carbolines in the +/+ mice. AC was less potent than the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.