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Evidence for Bile Acid Synthesis by Transplantable Hepatomas¹

Departments of Oncology and Pathology, McArdle Laboratory for Cancer Research [G. E. M., H. C. P.] and Department of Pathology, Medical School [S. G.], University of Wisconsin, Madison, Wisconsin 53706

Transplantable Morris hepatomas 5123C and 9618A were assayed for enzymes known to be active in the biosynthesis of bile acids in liver. Cholesterol 7-hydroxylase, the initial enzyme in the pathway of bile acid biosynthesis, was shown to be as active in 9618A tumor microsomes as in host liver microsomes. Activity of this enzyme in the 5123C tumor was about one-third that of host liver. 7-Hydroxycholesterol was shown to be metabolized by tumor microsomes to other probable intermediates. Cleavage of the sterol side chain, a part of the hepatic bile acid-metabolic pathway, was also detected in both 9618A and 5123C tumor mitochondrial preparations. Labeled chenodeoxycholic acid was identified in extracts from tumor and liver slices that were incubated in the presence of sodium mevalonate-³H.

¹ Supported by NIH Grant G-374-6, National Cancer Institute Grant CA-07175, and American Cancer Society Grant E-588.

² NIH Postdoctoral Fellow, Grant 1-F2-CA-52, 719-01. Present address: Departments of Pathology and Biochemistry, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284.

Received 9/21/73. Accepted 3/15/74.