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Bile Acid Involvement in Azo Dye Carcinogenesis¹

Department of Biological Sciences, Michigan Technological University, Houghton, Michigan 49931

3'-Methyl-4-dimethylaminoazobenzene was used to initiate the early stages of liver carcinoma development in Sprague-Dawley rats. Bile acids were analyzed in urine and feces of azo dye-fed and control rats with the use of gas chromatography during the first 66 days of treatment. Seven bile acids were identified in the feces, with deoxycholic acid being the primary excretion product. During the first 36 days of 3'-methyl-4-dimethylaminoazobenzene feeding, the feces showed little variation in bile acid concentration. During the same period, in a total of 112 assays on the urine of control rats, only two showed measurable quantities of bile acids. However, the urine of the dye-fed rats had significant amounts of cholic, hyodeoxycholic, and ursodeoxycholic acids. In three separate experiments, these acids consistently became elevated in the urine in the first 25 days of 3'-methyl-4-dimethylaminoazobenzene feeding. The results obtained were correlated with counts of oval cells in the liver with the use of standard histological procedures. The results showed a close correspondence between maximum urinary bile acid excretions and maximum oval cell proliferation rates, suggesting a relationship between urinary bile acid concentration and "oval cell" proliferation.

¹ This investigation was supported by American Cancer Society Grant E-217c.

Received 10/ 5/70. Accepted 1/19/71.