Cadmium's action on NRK-49F cells to produce responses induced also by TGF beta is not due to cadmium induced TGF beta production or activation.

Transforming growth factor beta (TGF beta) is a multifunctional regulator of cell growth that has either a stimulatory or inhibitory effect on cell proliferation, depending on TGF beta concentration and on cell type, history and culture conditions. Cadmium mimics some of the effects of TGF beta in cultured cells. In this study the effects of Cd2+ and TGF beta on EGF-induced DNA synthesis in a clonal subpopulation (N1) of NRK-49F cells were compared. It was found that TGF beta 1 and cadmium both inhibit EGF-induced DNA synthesis and cell proliferation in a dose-dependent fashion, but that neither inhibits EGF-induced myc oncogene accumulation. TGF beta 1 and cadmium added at the same time as EGF or several hours after EGF addition showed similar inhibitory effects on EGF-induced [3H]Tdr incorporation, indicating that the inhibitory effect of TGF beta 1 and cadmium on EGF-induced DNA synthesis does not involve early G1 events. Rather, they occur in late G1, at the G1/S boundary or during S phase. Because of the similarities in nature and timing of the Cd2+ and TGF beta responses, the possibility that Cd2+ acts through stimulation of TGF beta production and/or activation was explored. It is shown in this paper however that TGF beta neutralizing antibody blocks the effects of TGF beta 1, but not the cadmium effects, on EGF-induced DNA synthesis, suggesting that cadmium is not functioning through activation or preinduction of TGF beta.