This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shouval, D. Articles by Shafritz, D. A. Search for Related Content PubMed PubMed Citation Articles by Shouval, D. Articles by Shafritz, D. A.

Tumorigenicity in Nude Mice of a Human Hepatoma Cell Line Containing Hepatitis B Virus DNA¹

Liver Research Center [D. S., L. M. R., P. R. C., N. R-O., R. M., D. A. S.] and Departments of Molecular Pharmacology [L. M. R.], Pathology [R. M.], and Cell Biology [D. A. S.], Albert Einstein College of Medicine, Bronx, New York 10461, and Department of Pathology [M. A. G., S. N. T.], Mount Sinai School of Medicine, New York, New York 10029

The human hepatocellular carcinoma cell line PLC/PRF/5, which synthesizes and secretes hepatitis B surface antigen, was grown under optimal conditions in tissue culture, using Eagle's minimal essential medium supplemented with 10% fetal bovine serum and 10^-11 M triiodothyronine on collagen rafts. Injection s.c. of the PLC/PRF/5 cell line into athymic BALB/c nude mice resulted in the growth of a well-circumscribed, moderately differentiated hepatocellular carcinoma. The intervals until tumor appearance and tumor "take" rates were dependent on inoculum dose. Four to 5 x 10⁶ cells induced tumor growth in 29% of 14 injected mice within 29 to 40 days, while 7 to 13 x 10⁶ cells induced tumors in all 15 mice within 10 to 12 days after inoculation. Hepatitis B surface antigen was detected in the nude mouse serum and tumor tissue, and its concentration roughly correlated with tumor weight. A low level of antibody against hepatitis B surface antigen was detected in five tumor-bearing animals, as well as in one mouse which did not produce a tumor. Hepatitis B core antigen and its antibody and hepatitis B e antigen and its antibody were not detected in 26 mice, using immunohistochemical and radioimmunoassay methods. -Fetoprotein, carcinoembryonic antigen, and -antitrypsin were detected in nude mice tumors, using the peroxidase-antiperoxidase technique. Finally, hepatitis B virus DNA, identified in the nude mouse tumor by molecular hybridization techniques, was compared to PLC/PRF/5 cell line hepatitis B virus DNA.

¹ Research was supported in part by NIH Grants AM17609 and AM17702 and National Institute for Environmental Health Sciences Grant 2 P30 E 500928 06, American Cancer Society Institutional Grant IN-28U, American Cancer Society Grants BC-301 and PDT-131, and the Sara Chait Memorial Foundation.

² Recipient of an NIH J. F. Fogarty International Fellowship. On leave from Hadassah Hospital, Jerusalem, Israel. To whom requests for reprints should be addressed, at the Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, N. Y. 10461.

³ Recipient of a Sinnscheimer Career Development Award.

⁴ Recipient of Research Career Development Award A1 0035-05 from the USPHS.

Received 9/17/80. Accepted 12/30/80.