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Carcinogenesis Advance Access originally published online on September 11, 2003
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Carcinogenesis, Vol. 24, No. 12, 1913-1918, December 2003
© Oxford University Press; all rights reserved


MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains

Markus Zsivkovits, Kassie Fekadu, Gerhard Sontag1, Ursula Nabinger1, Wolfgang W. Huber, Michael Kundi2, Asima Chakraborty, Helmuth Foissy3 and Siegfried Knasmüller4

Institute of Cancer Research, Borschkegasse 8a, A-1090 Vienna, 1 Institute of Analytical Chemistry, Währinger Strasse 38, A-1090 Vienna, 2 Institute of Environmental Hygiene, Kinderspitalgasse 15, A-1090 Vienna and 3 Department of Dairy Research and Microbiology, Agricultural University, Gregor Mendel Strasse 33, A-1180 Vienna, Austria

The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef (‘beef mix’) and chicken (‘chicken mix’). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with a high consumption of LB-containing foods.


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C. Humblot, M. Murkovic, L. Rigottier-Gois, M. Bensaada, A. Bouclet, C. Andrieux, J. Anba, and S. Rabot
{beta}-Glucuronidase in human intestinal microbiota is necessary for the colonic genotoxicity of the food-borne carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline in rats
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