Regulation of the growth and production of granulocyte colony-stimulating activity (CSA) by WEHI-3 cells, a lysozyme-secreting mouse cell line adapted to culture, was investigated in vitro. WEHI-3 cloning efficiency is not enhanced by exogenously added CSA. However, WEHI-3 cloning efficiency in agar was suppressed by an activity in human polymorphonuclear neutrophil extract (colony-inhibiting activity) which inhibits endogenous WEHI-3 CSA production. The addition of increasing concentrations of WEHI-3- or L cell-conditioned medium containing CSA to CIA-depressed WEHI-3 agar cultures resulted in graded increases of cloning efficiency to that of the untreated sample. Testosterone, Deca-Durabolin, and bacterial lipopolysaccharide increased production of CSA by WEHI-3 cells and overcame colony-inhibiting activity-mediated suppression of CSA production, even when activating agents were added 1 day after the addition of colony-inhibiting activity. The activating agents had no direct stimulatory effect on normal mouse marrow colony-forming cells and did not enhance CSA activity. WEHI-3 cells respond to growth inhibitory and stimulatory activities and can serve as an in vitro model for studying the regulation of neoplastic cells.
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