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Department of Surgery [J-K. L.] and Medical Research [C-K. C.], Veterans General Hospital, and Graduate Institute of Clinical Medicine, National Yang-Ming Medical College [J-K. L., C-K. C.], Taipei, Taiwan
The effect of transforming growth factor ß1 (TGF-ß1) on human hepatoma cells (Hep 3B) was studied. Cell death was observed when the serum starved Hep 3B cells were exposed to a very low concentration of TGF-ß1. The half-maximal cytocidal concentration of TGF-ß1 was around 20 pM. Cell death began approximately 24 h following treatment, with more than 80% of the cells dying after 48 h. In contrast, the control cells, which were cultured in serum-free condition, still gradually proliferated. Furthermore, the cytocidal effect of TGF-ß1 on Hep 3B cells was not altered by either cycloheximide or actinomycin D. It was discovered, using diphenylamine assay, that TGF-ß1 induced DNA fragmentation in Hep 3B cells. Using gel electrophoresis, the fragmented DNA could be displayed, and showed a characteristic stepladder pattern. Thus, it appeared that TGF-ß1 induced a particular pathway in Hep 3B cells in which de novo protein synthesis was not actively involved, but endogenous nuclease was activated which cleaves cellular DNA and induces cell death.
1 To whom requests for reprints should be addressed, at Department of Medical Research, Veterans General Hospital-Taipei, 201, Section 2, Shih-Pai Road, Shih-Pai, Taipei, 11217, Taiwan.
Received 8/ 1/91. Accepted 11/ 1/91.
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