Article

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

Institute of Cancer Research, Borschkegasse 8a, A-1090 Vienna, Austria.
Carcinogenesis (Impact Factor: 5.64). 11/2001; 22(10):1721-5. DOI:10.1093/carcin/22.10.1721
Source: PubMed

ABSTRACT 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.

0 0
 · 
0 Bookmarks
 · 
30 Views
  • [show abstract] [hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is the most common gastrointestinal cancer, and a significant health care problem globally. Dietary factors, for example high meat consumption and deficiency of fiber, calcium, vitamin D, and folate, are well-recognized to be associated with a risk of developing CRC. Colonic microbiota, by living in a mutual relationship and participating in key metabolic functions that compliment host physiology, is crucially important in the maintenance of our health. A state of imbalance in host–microbe homeostasis, termed dysbiosis, is associated with several diseases, including CRC. Epidemiological studies have revealed strong associations between diet, microbiota, and CRC. Substantial in-vitro and in-vivo evidence suggests that the dynamic composition and diversity of colonic microbiota are affected by alteration of the diet, and that the balance between the beneficial and detrimental microbial metabolites is of crucial importance in mediation of the dietary risk factors of colonic carcinogenesis. A better understanding of complex diet–microbiota–CRC relationships can help us understand how diet affects the risk of CRC and will provide a more scientific approach to the development of novel strategies to prevent CRC.
    Current Colorectal Cancer Reports 01/2013;
  • [show abstract] [hide abstract]
    ABSTRACT: Microbiota and host form a complex 'super-organism' in which symbiotic relationships confer benefits to the host in many key aspects of life. However, defects in the regulatory circuits of the host that control bacterial sensing and homeostasis, or alterations of the microbiome, through environmental changes (infection, diet or lifestyle), may disturb this symbiotic relationship and promote disease. Increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis. In this Opinion article, we discuss links between the bacterial microbiota and cancer, with a particular focus on immune responses, dysbiosis, genotoxicity, metabolism and strategies to target the microbiome for cancer prevention.
    Nature Reviews Cancer 10/2013; · 29.54 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Obesity is a critical health concern and although genetic factors may predispose an individual to become obese, changes in diet and lifestyle over the last few decades are likely to be significant contributors. Even so, it has been suggested that the causes of the current obesity crisis are not simply explained by changes in eating and exercise habits. Evidence suggests that the gut microbiota may play an important role in obesity and may be a factor in the development of associated disease including diabetes, CVD, non-alcoholic fatty liver disease and cancer. There have been tremendous advances in knowledge regarding the composition of human gut microbiota, but less is known about their function and role within the human host. It is becoming widely accepted that the products of microbial metabolism influence human health and disease, particularly with respect to immune response and inflammation. However, in most cases, the products of microbial metabolism are uncharacterised and their mechanism of action remains unknown. This review addresses the role of the metabolites produced by gut microbiota in cancer and obesity. It is clear that only if the link between microbial diversity and metabolic functionality is firmly established, will the mechanism by which gut microbiota maintains health or contributes to disease development be elucidated.
    Proceedings of The Nutrition Society 11/2012; · 3.67 Impact Factor