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Effect of 5-Fluorouracil on the Release of Thymidine Kinase from Hepatoma Cells in Vitro¹

Department of Radiology, Division of Nuclear Medicine, Veterans Administration Medical Center, University of California, San Diego, San Diego, California 92161, and Department of Medicine, Division of Medical Genetics, University of California, San Diego, La Jolla, California 92093

Cells of the Morris hepatoma 7777 cultured in vitro have elevated levels of cytoplasmic thymidine kinase similar to those found in vivo. The cell-doubling time is slightly less than 24 hr. The addition of 5-fluorouracil to the culture medium (10 µg/ml) inhibits cell division, stimulates thymidine kinase production, and results in cell death which increases with time. Treated cells release significantly (p 0.01) more thymidine kinase into the culture medium than do untreated cells, and this effect can also be seen following a 60-min pulsed incubation of the cells with 5-fluorouracil. The total activity of thymidine kinase released is proportional to cell death and to the number of cells originally on the plate. These results suggest the possibility of monitoring tumor response to therapy in vivo by measuring serum levels of thymidine kinase.

¹ This study was supported by the Veterans Administration, Veterans Administration Medical Center, San Diego, Calif., and by USPHS Grant GM 17701, Human Biochemical Genetics Program.

² To whom requests for reprints should be addressed, at Nuclear Medicine Service (115), Veterans Administration Medical Center, 3350 La Jolla Village Drive, San Diego, Calif. 92161.

Received 11/17/79. Accepted 10/ 9/80.