Journal Article

The food mutagen 2-amino-9<i>H</i>-pyrido[2,3-<i>b</i>]indole (AαC) but not its methylated form (MeAαC) increases intestinal tumorigenesis in neonatally exposed multiple intestinal neoplasia mice

Inger-Lise Steffensen, Jan Erik Paulsen and Jan Alexander

in Carcinogenesis

Volume 23, issue 8, pages 1373-1378
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.8.1373
The food mutagen 2-amino-9H-pyrido[2,3-b]indole (AαC) but not its methylated form (MeAαC) increases intestinal tumorigenesis in neonatally exposed multiple intestinal neoplasia mice

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The heterocyclic amines 2-amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC) are carcinogenic in several organs in rodents, but not in the intestinal tract. However, AαC induces DNA adducts, mutations and preneoplastic aberrant crypt foci (ACF) in rodent colons. The purpose of this study was to examine whether AαC and MeAαC 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 AαC (40.3 mg/kg) or MeAαC (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. AαC 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 AαC exposure appeared to be smaller than the spontaneous lesions, indicating later induction, slower growth or both. In contrast to AαC, MeAαC did not affect intestinal tumorigenesis in Min/+ mice. No effects were found by any of the amino-α-carbolines in the +/+ mice. AαC was less potent than the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Keywords: AαC, 2-amino-9H-pyrido[2,3-b]indole; AC, aberrant crypt; ACF, aberrant crypt foci; APC/Apc, adenomatous polyposis coli gene, human/murine; DMSO, dimethylsulfoxide; FAP, familial adenomatous polyposis; IQ, 2-amino-3-methylimidazo[4,5-f]quinoline; MeAαC, 2-amino-3-methyl-9H-pyrido[2,3-b]indole; Min, multiple intestinal neoplasia; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Journal Article.  5479 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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