EFFECT OF GROWTH-FACTORS AND ANTITUMOR DRUGS ON NORMAL AND VA12 HA-RAS TRANSFORMED C3H 10T1 2 CELL TRANSPLASMA MEMBRANE ELECTRON-TRANSPORT AND GROWTH/

Both ras and the transplasma membrane electron transport system have b een implicated in the control of cell growth. Since the loss of growth regulation is at the heart of the cancerous phenotype, we have invest igated the effect of factors like antitumor drugs, which inhibit cell growth, and growth factors which either cause or prepare the cells for growth. We have found that growth factors increase the plasma membran e electron transport of the normal cells but not that of the cells whi ch have been transfected with oncogenic ras (which have a 2-5-fold fas ter basal rate). In the presence of adriamycin the activity of the ele ctron transport system is and cell numbers are decreased more in norma l cells than in the cells which have been transfected with the oncogen ic version of the Harvey ras gene. Cisplatin inhibits cell growth but does not inhibit ferricyanide reduction. Ferricyanide alone or in conj unction with EGF or TPA does not stimulate cell proliferation with eit her cell line in the absence of fetal calf serum, so simple activation of plasma membrane electron transport is not sufficient to activate a complete growth response.