Intestinal microflora plays a crucial role in the genotoxicity of the cooked food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)

University of Vienna, Wien, Vienna, Austria
Carcinogenesis (Impact Factor: 5.33). 11/2001; 22(10):1721-5. DOI: 10.1093/carcin/22.10.1721
Source: PubMed


We investigated the impact of the intestinal microflora on the genotoxicity of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), a mutagenic/carcinogenic heterocyclic amine commonly found in fried meats and fish. In parallel, we also examined the effect of the microflora on the protective effect of glucotropaeolin (GT), a glucosinolate contained in cruciferous vegetables, towards IQ-induced genotoxic effect. Conventional (NF), human flora associated (HFA) and germ free (GF) rats were treated either with 90 mg/kg IQ alone, 150 mg/kg GT alone or a combination of the two by gavage and DNA damage was determined in liver and colon cells using the alkaline single cell gel electrophoresis (SCGE) or comet assay. IQ caused a significant effect in both organs of all groups. However, DNA damage was most pronounced in NF animals. In colon cells, DNA migration was 6-fold more in IQ-exposed rats as compared with untreated controls. The effect measured with liver cells was similar. In comparison to NF rats, in HFA rats, tail length of the comets was 22 and 53% lower in liver and colon cells, respectively. Significantly weaker effects were seen in GF animals (66 and 75% lower damage in hepatocytes and colonocytes, respectively, than in NF animals). Pretreatment with GT led to a complete reduction of IQ-induced DNA damage regardless of the microbial status of the animals. In addition, a moderate decrease in spontaneous DNA damage was seen in animals that received GT alone. Our results show that the microflora has a strong impact on the genotoxic effects of IQ. We conclude that the alkaline SCGE assay with rats harbouring different flora opens new possibilities to investigate the role of intestinal bacteria on health risks caused by dietary carcinogens.

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    • "Anaerobic colonic bacteria, such as Eubacterium spp., have the capacity to convert IQ to 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline-7-one (HOIQ), which is a known mutagen (Bashir et al., 1987; Carman et al., 1988). IQ induces DNA mutations , sister chromatid exchanges, unscheduled DNA synthesis, and DNA adduct formation (Holme et al., 1987; Kassie et al., 2001; Wild et al., 1986). In another example of how bacterial metabolites may influence CRC development, commensal bacteria of the Bacteroides genus generate ether-like polyunsaturated lipids such as fecapentaenes (de Kok et al., 1992), and a number of in vitro and in vivo studies have confirmed that fecapentaenes induce oxidative DNA damage through generation of 8-oxo-dG or directly alkylate DNA to form secondary mutagenic species (Huycke and Gaskins, 2004; Shioya et al., 1989; Zarkovic et al., 1993). "
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