Sensitivity of the cell cycle to TGF beta 1 does not correlate with transformation of a rat liver epithelial cell line.

The effects of TGF beta 1 on cell cycle events in a rat liver derived epithelial cell line (BL9) and in two in vitro transformants of this line were studied by flow cytometry. Using either ethidium bromide staining or the incorporation of bromodeoxyuridine to evaluate DNA synthesis it was shown that TGF beta 1 prevented the entry of G0/G1 phase BL9 cells into S phase. TGF beta 1 did not exert its inhibitory effect(s) on DNA synthesis by the modulation of early events in the cell cycle. The tumorigenic transformed BL9 cell lines gave contrasting responses to the effects of TGF beta 1. DNA synthesis in a BL9 cell line derived by transfection with an active N-ras oncogene was unaffected by TFG beta 1 and thus appeared refractory to its growth controlling effects. On the other hand cells from a BL9 cell line derived by in vitro transformation with activated aflatoxin B1 retained their sensitivity to the effects of TGF beta 1. Thus the loss of the inhibitory effect of TGF beta 1 on DNA synthesis is not obligatory for the malignant transformation of rat liver epithelial cells.