Damaging Effect of Dietary Components to Colon Epithelial Cells In Vivo: Effect of Mutagenic Heterocyclic Amines2

Abstract

The nuclear damaging effects of the mutagenic heterocyclic amines 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole [(Trp-P-1) CAS: 62450-06-0; 1,4-dimethyl-5H-pyrido(4,3-b)indol-3-amine], 3-amino-1-methyl-5H-pyrido(4,3-b)indole [(Trp-P-2) CAS: 62450-07-1; 1-methyl-5H-pyrido(4,3-b)indol-3-amine], 2-amino-6-methyldipyrido(1,2-a:3′,2′-d)imidazole [(Glu-P-1) CAS: 67730-11-4; 6-methyldipyrido(1,2-a:3′,2′-d)imidazol-2-amine], 2-amino-3-methylimidazo(4,5-f)quinoline [(IQ) CAS: 76180-96-6; 3-methyl-3H-imidazo(4,5-f)quinolin-2-amine], and 2-amino-3,4-di-methylimidazo(4,5-f)quinoline (MelQ) on colon epithelial cells of C57BL/6J mice were investigated. The numbers of nuclear aberrations (NA) per crypt was determined 24 hours after oral administration of these amines at various dose levels. Trp-P-1, Trp-P-2, and Glu-P-T increased the incidence of NA approximately twofold to threefold above the background level (0.15 NA/crypt) even at near-lethal dose levels. However, IQ and MelQ increased the incidence fivefold to tenfold at nonlethal dose levels ranging from 200 to 800 mg/kg body weight and from 50 to 200 mg/kg body weight, respectively. IQ intubation in the morning (11 a.m.) produced the maximum response in 24 hours, whereas intubation in the evening (7 p.m.) produced maximum response in 12 hours. The colon-specific toxicity of the heterocyclic amines at approximately 35% of their maximum tolerated dose levels was in the order of MelQ>IQ>Trp-P-2>Trp-P-1≥Glu-P-1.