Lithocholic acid, a monohydroxy secondary bile acid, is present in tissues in two forms. One form is extractable with 95% ethanol-0.1% ammonia (soluble lithocholate), and the other form is firmly bound to tissue residues and can be released only by the bile salt-deconjugating enzyme, clostridial cholanoylamino acid hydrolase (tissue-bound lithocholate). Studies on bile salt-protein interactions revealed that lithocholic acid had amino group-modifying activity specifically directed against the basic side group of lysine residues. Degradative procedures yielded N-ε-lithocholyllysine, confirmed by comparison with the authentic compound synthesized in our laboratories. Studies on the distribution of tissue-bound lithocholate in tissues have revealed high concentrations of this form of lithocholate in livers of rats treated with the carcinogen, methylazoxymethanol. In light of these observations, the role of bile acids, and specifically lithocholic acid, as promoters of tumorigenesis must be further investigated.


Presented at the Workshop on Fat and Cancer, December 10 to 12, 1979, Bethesda, Md.

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