Transforming growth factor beta inhibits DNA synthesis in hepatocytes isolated from normal and regenerating rat liver
Strain, A.J.; Frazer, A.; Hill, D.J.; Milner, R.D.
Biochemical and Biophysical Research Communications 145(1): 436-442
1987
ISSN/ISBN: 0006-291X PMID: 3473988 Document Number: 300833
The inhibitory action of transforming growth factor .beta. (TGF.beta.) on DNA synthesis in hepatocytes isolated from the liver of normal rats or from the liver remnant of rats 18 h following partial hepatectomy was compared. Continuous exposure to TGF.beta. inhibited DNA synthesis of cultured hepatocytes to a similar degree in both groups when labelled with 3H thymidine from 24-48 h or 48-72 h. At 20 pM TGF.beta., 3H-thymidine incorporation was reduced by 64-78% in hepatocytes from normal liver and by 60-73% in cells from 18 h regenerating liver. The nuclear labelling index was reduced by 70-80% in all cells. Exposure to TGF.beta. at concentrations up to 500 pM from 0-24 h had no effect on 3H-thymidine incorporation, but exposure at 20 pM for 24 h periods thereafter was uniformally effective. These results indicate that there is no change in sensitivity of hepatocytes from 18 h regenerating liver to TGF.beta., compared with normal cells, and that TGF.beta. may act at some point in the G1 phase of the cell cycle to inhibit hepatocyte growth.