Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide

Mölzer, Christine, Huber, Hedwig, Steyrer, Andrea, Ziesel, Gesa V., Wallner, Marlies, Hong, Hung T., Blanchfield, Joanne T., Bulmer, Andrew C. and Wagner, Karl-Heinz (2013) Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide. Journal of Natural Products, 76 10: 1958-1965. doi:10.1021/np4005807


Author Mölzer, Christine
Huber, Hedwig
Steyrer, Andrea
Ziesel, Gesa V.
Wallner, Marlies
Hong, Hung T.
Blanchfield, Joanne T.
Bulmer, Andrew C.
Wagner, Karl-Heinz
Title Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide
Journal name Journal of Natural Products   Check publisher's open access policy
ISSN 0163-3864
1520-6025
Publication date 2013-10-25
Sub-type Article (original research)
DOI 10.1021/np4005807
Volume 76
Issue 10
Start page 1958
End page 1965
Total pages 8
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2014
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 22 Nov 2013, 21:57:03 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences