TY - JOUR
T1 - Impact of bacteria in dairy products and of the intestinal microflora on the genotoxic and carcinogenic effects of heterocyclic aromatic amines
AU - Knasmüller, Siegfried
AU - Steinkellner, Hans
AU - Hirschl, Alexander M.
AU - Rabot, Sylvie
AU - Nobis, Eva C.
AU - Kassie, Fekadu
N1 - Funding Information:
The experimental work was supported by a EU-grant (HC-amines, QLRT-1999-01197).
PY - 2001/9/1
Y1 - 2001/9/1
N2 - This article gives a short overview on the present state of knowledge of the effects of the intestinal microflora on the health hazards of heterocyclic aromatic amines (HAs). Results of single cell gel electrophoresis assays with conventional, germ free and human flora associated rats indicate that the presence of intestinal microorganisms strongly enhances the induction of DNA-damage in colon and liver cells by IQ. Furthermore, it was found that supplementation of the feed with Lactobacilli attenuates the induction of colon cancer by this same amine. These recent findings suggest that the intestinal microflora and lactic acid bacilli in dairy products strongly affect the health risks of HAs. Nevertheless, most previous experiments with HAs focused on the involvement of mammalian enzymes in the biotransformation of these compounds and only a few articles are available which concern interactions of bacteria with HAs. Some of these studies suggested that the formation of directly mutagenic hydroxy-metabolites of the amines by fecal bacteria might be an important activation pathway but it turned out that the hydroxy-derivative of IQ is not genotoxic in mammalian cells and does not cause colon cancer in laboratory rodents. There is some evidence that hydrolysis of HA-metabolites by bacterial β-glucuronidase might play a role in the activation of HAs but experimental data are scarce and no firm conclusions can be drawn at present. The most important detoxification mechanism appears to be the direct binding of the HAs to the cell walls of certain bacterial strains contained in fermented foods. It was shown that these effects do also take place under physiologically relevant conditions. Overall, it seems that intestinal bacteria play a key role in the activation and detoxification of HAs which has been an area of research long ignored. The elucidation of these mechanisms may enable the development of biomarkers for colon cancer risk and nutritional strategies of protection.
AB - This article gives a short overview on the present state of knowledge of the effects of the intestinal microflora on the health hazards of heterocyclic aromatic amines (HAs). Results of single cell gel electrophoresis assays with conventional, germ free and human flora associated rats indicate that the presence of intestinal microorganisms strongly enhances the induction of DNA-damage in colon and liver cells by IQ. Furthermore, it was found that supplementation of the feed with Lactobacilli attenuates the induction of colon cancer by this same amine. These recent findings suggest that the intestinal microflora and lactic acid bacilli in dairy products strongly affect the health risks of HAs. Nevertheless, most previous experiments with HAs focused on the involvement of mammalian enzymes in the biotransformation of these compounds and only a few articles are available which concern interactions of bacteria with HAs. Some of these studies suggested that the formation of directly mutagenic hydroxy-metabolites of the amines by fecal bacteria might be an important activation pathway but it turned out that the hydroxy-derivative of IQ is not genotoxic in mammalian cells and does not cause colon cancer in laboratory rodents. There is some evidence that hydrolysis of HA-metabolites by bacterial β-glucuronidase might play a role in the activation of HAs but experimental data are scarce and no firm conclusions can be drawn at present. The most important detoxification mechanism appears to be the direct binding of the HAs to the cell walls of certain bacterial strains contained in fermented foods. It was shown that these effects do also take place under physiologically relevant conditions. Overall, it seems that intestinal bacteria play a key role in the activation and detoxification of HAs which has been an area of research long ignored. The elucidation of these mechanisms may enable the development of biomarkers for colon cancer risk and nutritional strategies of protection.
KW - Carcinogenicity
KW - Genotoxicity
KW - Heterocyclic aromatic amines
KW - Intestinal bacteria
KW - Lactic bacilli
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U2 - 10.1016/S0027-5107(01)00176-2
DO - 10.1016/S0027-5107(01)00176-2
M3 - Article
C2 - 11506806
AN - SCOPUS:0035451824
SN - 0027-5107
VL - 480-481
SP - 129
EP - 138
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
ER -