PMID- 2015607 OWN - NLM STAT- MEDLINE DCOM- 19910517 LR - 20151119 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 51 IP - 9 DP - 1991 May 1 TI - Effect of transforming growth factor beta on cell death of cultured rat hepatocytes. PG - 2478-85 AB - We investigate mechanisms of regression of liver hyperplasia which occurs after induction of growth by hepatomitogens and their subsequent withdrawal. We hypothesized that transforming growth factor beta 1 (TGF-beta 1) might be involved in the control of regression. Therefore we studied the effect of this agent on DNA synthesis and death of hepatocytes cultured in vitro. Both the low basal rate of DNA synthesis of untreated cells and its increase by epidermal growth factor (10 ng/ml) were suppressed by TGF-beta 1 at concentrations higher than 0.01-0.1 ng/ml. At the same range of concentrations of TGF-beta 1, the DNA content of the cultures declined significantly and numerous dead cells could be seen in the monolayer. Time course studies showed that TGF-beta 1 (1 ng/ml) decreased DNA content in the cultures linearly to 41 +/- 7% of controls during a period of 48 h. A similar decrease occurred with vital hepatocytes in hematoxylin and eosin stained monolayers. These changes were accompanied by an extensive release of lactate dehydrogenase which began at 20 h and was 70% of the total lactate dehydrogenase content of the cultures at 40-48 h. Little formation of guanidine hydrochloride resistant bodies and no fragmentation of DNA, indicators of apoptotic cell death, were detected after TGF-beta 1 (1 ng/ml) treatment. Time lapse cinematography revealed an active detachment of the cells from the underlying collagen gel. These studies show that inhibition of DNA synthesis by TGF-beta 1 is associated with enhanced cell death in cultured hepatocytes. FAU - Oberhammer, F AU - Oberhammer F AD - Institut fur Tumorbiologie-Krebsforschung Universitat Wien, Vienna, Austria. FAU - Bursch, W AU - Bursch W FAU - Parzefall, W AU - Parzefall W FAU - Breit, P AU - Breit P FAU - Erber, E AU - Erber E FAU - Stadler, M AU - Stadler M FAU - Schulte-Hermann, R AU - Schulte-Hermann R LA - eng PT - Journal Article PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Biomarkers) RN - 0 (Transforming Growth Factor beta) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Biomarkers MH - Cell Division MH - Cell Survival/*drug effects MH - Cells, Cultured MH - DNA/*biosynthesis MH - Dose-Response Relationship, Drug MH - Epidermal Growth Factor/pharmacology MH - Female MH - Liver/*cytology/metabolism MH - Rats MH - Rats, Inbred F344 MH - Time Factors MH - Transforming Growth Factor beta/*pharmacology EDAT- 1991/05/01 00:00 MHDA- 1991/05/01 00:01 CRDT- 1991/05/01 00:00 PHST- 1991/05/01 00:00 [pubmed] PHST- 1991/05/01 00:01 [medline] PHST- 1991/05/01 00:00 [entrez] PST - ppublish SO - Cancer Res. 1991 May 1;51(9):2478-85.