Schadstoffe hausgemacht

Zusammenfassung

Epidemiologische Studien zeigen, dass der Verzehr von stark erhitztem roten Fleisch das Dickdarmkrebsrisiko erhöht. Rotes Fleisch enthält hohe Konzentrationen an Häm, das die Bildung von N-Nitrosoverbindungen im Darm fördert, insbesondere von Nitrosyl-Häm und S-Nitrosothiolen. Diese Verbindungen lassen sich nach dem Verzehr von rotem Fleisch im Stuhl nachweisen. Treffen Nitrosyl-Häm und S-Nitrosothiole im Darm auf die Aminosäure Glycin, entsteht das reaktive Agens Diazoazetat, das zur Modifizierung von DNA-Basen in Dickdarmepithelzellen führt. Unklar ist zum jetzigen Zeitpunkt, ob diese DNA-Addukte langfristig zur Entstehung von Dickdarmkrebs führen können.

Abstract

Epidemiological studies have shown that consumption of red meat that has been heated very strongly increases the risk of cancer of the large intestine. Red meat contains high concentrations of haem, which promotes the development of N-nitroso compounds in the large bowel, especially of nitrosyl haem and S-nitrosothiols. These compounds are found in faeces after consumption of meat; their amount depends on the quantity of meat eaten. If nitrosyl haem and S-nitrosothiols react with the amino acid glycine in the intestine, the reactive agent diazoacetate is formed, which in turn leads to modifications of the DNA bases in the epithelium of the large intestine. It is not clear whether these adducts contribute to the development of colon cancer in the long term.

Schlüsselwörter

Dickdarmkrebs - rotes Fleisch - Häm - endogen gebildete N-Nitrosoverbindungen - modifizierte DNA-Basen

Keywords

cancer of the large intestine - red meat - haem - endogenous formation of N-nitroso compounds - modified DNA bases

Literatur

• 1 Scheppach W, Bingham S, Boutron-Ruault M C. et al . WHO consensus statement on the role of nutrition in colorectal cancer.  Eur J Cancer. 1999;  Prev. 8 57-62
• 2 Cross A J, Sinha R. Meat-related mutagens / carcinogens in the etiology of colorectal cancer.  Environ Mol Mutagen. 2004;  44 44-55
• 3 Norat T, Bingham S, Ferrari P. et al . Meat, fish and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition.  J Natl Cancer Inst. 2005;  97 906-916
• 4 Bingham S A, Hughes R, Cross A J. Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response.  J Nutr. 2002;  132 3522S-3525S
• 5 Hughes R, Cross A J, Pollock J RA. et al . Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation.  Carcinogenesis. 2001;  22 199-202
• 6 Cross A J, Pollock J RA, Bingham S A. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat.  Cancer Res. 2003;  63 2358-2360
• 7 Lunn J C, Kuhnle G, Mai V. et al . The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract.  Carcinogenesis. 2007;  28 685-690
• 8 Calmels S, Ohshima H, Vincent P. et al . Screening of microorganisms for nitrosation catalysis at pH 7 and kinetic studies on nitrosamine formation from secondary amines by E. coli strains.  Carcinogenesis. 1985;  6 911-915
• 9 Cupid B C, Zeng Z, Singh R. et al . Detection of O6-carboxymethyl-2'-deoxyguanosine in DNA following reaction of nitric oxide with glycine and in human blood DNA using a quantitative immunoslot blot assay.  Chem Res Toxicol. 2004;  17 294-300
• 10 Lewin M H, Bailey N, Bandaletova T. et al . Red meat enhances the colonic formation of the DNA adduct O6-carboxymethyl guanine: implications for colorectal cancer risk.  Cancer Res. 2006;  66 1859-1865
• 11 Shuker D EG, Margison G P. Nitrosated glycine derivatives as a potential source of O6-methylguanine in DNA.  Cancer Res. 1997;  57 366-369