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.