Natureof Tissue-bound LithocholicAcidand Its Implicationsin the Roleof BileAcidsin Carcinogenesis1

Lithocholic acid, a monohydroxy secondary bile acid, is present in tissues in two forms. One form is extractable with 95% ethanol-O.1% ammonia (soluble lithocholate), and the other form is firmly bound to tissue residues and can be releasedonlybythebilesalt-deconjugating enzyme,clostridial cholanoylamino acid hydrolase (tissue-bound lithocholate). Studleson bile salt-protein interactionsrevealedthat lithocholic acid had amino group-modifying activity specifically directed against the basic side group of lysine residues. Degradative proceduresyieldedN-€-lithocholyllysine, confirmedby com panson with the authentic compound synthesized in our labo ratories. Studies on the distribution of tissue-boundlithocholate in tissues have revealed high concentrations of this form of lithocholate in livers of rats treated with the carcinogen, meth ylazoxymethanol.In light of these observations,the role of bile acids,andspecifically lithocholic acid,aspromoters oftumor igenesis must be further investigated.