title: Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide.
abstract: Bilirubin exhibits antioxidant and antimutagenic effects in vitro. Additional tetrapyrroles that are naturally abundant were tested for antigenotoxicity in Salmonella. Un-/conjugated bilirubin (1 and 2), biliverdin (4), bilirubin and biliverdin dimethyl esters (3 and 5), stercobilin (6), urobilin (7), and protoporphyrin (8) were evaluated at physiological concentrations (0.01-2 μmol/plate; 3.5-714 μM) against the metabolically activated food-borne mutagens aflatoxin B1 (9) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (10). Compound 8 most effectively inhibited the mutagenic effects of 9 in strain TA102 and 10 in TA98. Compound 7 inhibited 9-induced mutagenesis in strain TA98 most effectively, while 1 and 4 were promutagenic in this strain. This is likely due to their competition with mutagens for phase-II detoxification. Mechanistic investigations into antimutagenesis demonstrate that tetrapyrroles react efficiently with a model epoxide of 9, styrene epoxide (11), to form covalent adducts. This reaction is significantly faster than that of 11 with guanine. Hence, the evaluated tetrapyrroles inhibited genotoxicity induced by poly-/heterocyclic amines found in foods, and novel evidence obtained in the present investigation suggests this may occur via chemical scavenging of genotoxic metabolites of the mutagens investigated. This may have important ramifications for maintaining health, especially with regard to cancer prevention.
authors.affiliation: Department of Nutritional Sciences, Emerging Field Oxidative Stress and DNA Stability, Faculty of Life Sciences, University of Vienna , Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Mölzer
authors.forename: Hedwig
authors.initials: H
authors.lastname: Huber
authors.forename: Andrea
authors.initials: A
authors.lastname: Steyrer
authors.forename: Gesa V
authors.initials: GV
authors.lastname: Ziesel
authors.forename: Marlies
authors.initials: M
authors.lastname: Wallner
authors.forename: Hung T
authors.initials: HT
authors.lastname: Hong
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Blanchfield
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Bulmer
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
mesh_terms: D016604:Aflatoxin B1 / Q000737:chemistry / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001663:Bilirubin / Q000737:chemistry / Q000494:pharmacology*; D001664:Biliverdine / Q000737:chemistry / Q000494:pharmacology*; D005502:Food; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D045725:Tetrapyrroles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016587:Antimutagenic Agents; D000975:Antioxidants; D009153:Mutagens; D045725:Tetrapyrroles; D016604:Aflatoxin B1; D001664:Biliverdine; D001663:Bilirubin