Structure-activity relationship amongst biliary acids showing comutagenic activity towards 1,2-dimethylhydrazine.
Secondary biliary acids act, in vitro, as co-mutagenic agents towards 1,2-dimethylhydrazine incubated in the presence of Salmonella typhimurium strain TA 100. The present report demonstrates an important structure-activity relationship with regard to this effect. The number and position of hydroxyl substituents, the configuration at various C atoms and the stereochemistry of the junction between rings A and B of the steroid moiety are parameters which influence the cogenotoxic activity. Beyond these structural parameters, the basic physico-chemical properties of the biliary acids could be the key factor controlling their effects. Co-incubation of the various biliary acids reveals that the so-called secondary compounds antagonise each other's activity; moreover, in the presence of a constant concentration of primary bile acids, the co-mutagenic effect is directly related to the amount of the secondary bile acids. The co-mutagenic activity of the secondary biliary acids and its modulation by their mixing could be a key factor in the etiology of colon cancer.
D019813:1,2-Dimethylhydrazine; D001647:Bile Acids and Salts / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003840:Deoxycholic Acid / Q000494:pharmacology; D004127:Dimethylhydrazines / Q000494:pharmacology*; D004347:Drug Interactions; D008095:Lithocholic Acid / Q000494:pharmacology; D008763:Methylhydrazines / Q000494:pharmacology*; D008968:Molecular Conformation; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D009153:Mutagens; D003840:Deoxycholic Acid; D008095:Lithocholic Acid; D019813:1,2-Dimethylhydrazine