Interaction between TNFone and tetrapyrroles may account for their anti-genotoxic effects — a novel mechanism for DNA-protection

Autoren:Mölzer, Christine; Wallner, Marlies; Goncharova, Iryna (University of Chemistry and Technology, Prague); Orlov, Sergey (University of Chemistry and Technology, Prague); Urbanová, Marie (University of Chemistry and Technology, Prague); Ahlfors, Charles E. (Stanford University); Vítek, Libor (Charles University Prague); Bulmer, Andrew Cameron (Griffith University); Wagner, Karl-Heinz
Abstrakt:Bilirubin, the principal and biologically most relevant bile pigment was, until recently, considered a waste product of haem catabolism. However, current data suggest that bile pigments possess biological potential, related to their antioxidant and anti-mutagenic effects. In this context, it is now assumed that bile pigments and their derivatives exert these effects via multiple mechanisms, including discrete anti-oxidative and physico-chemical interactive effects. The major scientific focus so far has concentrated on the compounds' antioxidant action, and mechanistic investigations of possible mutagen-tetrapyrrole interaction are lacking. Therefore we tested structurally related bile pigments/derivatives (bilirubin/-ditaurate/-dimethyl ester, biliverdin/-dimethyl ester, urobilin, stercobilin and protoporphyrin) for anti-genotoxicity in the Salmonella reverse mutation assay (strains TA98, TA102), together with the synthetic mutagen 2,4,7-trinitro-9H-fluoren-9-one (TNFone). To explore possible structural interactions, molecular systems of chlorin e6 porphyrin/bilirubin/biliverdin with TNFone were assayed using circular dichroism. These data consistently revealed, at suprastoichiometric concentrations, that tetrapyrroles interact with TNFone. Addition of TNFone to chlorin e6 porphyrin, bilirubin-albumin and biliverdin-albumin led to a marked change in pigment spectra, providing evidence for tight tetrapyrrole-mutagen interaction. This conclusion was also supported by substantial, TNFone-induced decrease of bilirubin oxidation in the bilirubin-albumin system. This outcome was reflected in a bacterial model, in which most tetrapyrroles and especially protoporphyrin, significantly attenuated TNFone-induced mutagenesis. These data indicate that aromatic, tetrapyrrolic molecules interact with TNFone, providing a novel mechanism to suggest the anti-mutagenic effects of bile pigments in vivo are related to their physico-chemical interaction with genotoxins. Read More: http://www.worldscientific.com/doi/abs/10.1142/S1088424613500995
Sprache:Englisch
Anzahl der Seiten:10
Publikationsdatum:12.2013
Journaltitel:Journal of Porphyrins and Phthalocyanines
Volume:17
Nummer:12
Seiten:1-10
Peer reviewed:true
Links:
Digital Object Identifier (DOI):http://dx.doi.org/10.1142/S1088424613500995
Publikationstyp:Artikel
Portal:https://ucris.univie.ac.at/portal/en/publications/interaction-between-tnfone-and-tetrapyrroles-may-account-for-their-antigenotoxic-effects--a-novel-mechanism-for-dnaprotection(a1b2b609-fbbf-4932-b34b-d29a5ec7ebad).html