A Cancerogenic Extract from Human Bile and Gall Bladders. ∗

The possibility that human bile might contain substances which have cancerogenic activity was suggested by the discovery that a powerful cancerogen, methylcholanthrene, could be made from bile acids,^1-3 by the incidence of carcinoma of the biliary system, where comparatively few cells give rise to numerous tumors, and by discovery that extracts of human liver have cancerogenic activity. 4 Some of this material might be excreted in the bile and induce tumors in the biliary passages, and in the gastrointestinal tract.

Human bile has not previously been reported to induce sarcomas at the site of injection. Using ox bile, Turner 5 induced 1 sarcoma in 75 mice that lived over 34 weeks. Bürger and Uiker 6 induced only leukemialike changes in the liver and spleen of mice with an emulsion of human bile. Neufach and Shabad 7 also induced no tumors at the site of injection of a benzene extract of human bile, but stated that the incidence of various tumors in distant organs was greater than in controls.

Methods. Human gall bladder bile and some of the gall bladders from which it was obtained were collected from adults. Approximately 40% of these persons died with malignant tumors. The dried residue, weighing 2400 g, was saponified with alcoholic potassium hydroxide by refluxing on a steam bath for 24 hr. After repeated extractions with ethylene dichloride the extracts were combined and dried over anhydrous sodium sulfate. The extract was then filtered and the ethylene dichloride distilled in partial vacuum. The residue was resaponified with alcoholic potassium hydroxide for 4 hr, and then extracted, dehydrated, filtered, and distilled as before. The nonsaponifiable residue weighed 38.5 g.