Resistance of African green monkey kidney cell lines to actinomycin D: drug uptake in 37 RC cells after persistent inhibition of transcription

Abstract

37 RC cells, a cultured line derived from African green monkey kidneys, survived long treatments with actinomycin D (AMD; 0.1 to 0.5 mug/ml) under strong inhibition of ribonucleic acid synthesis and blocking of cell division. One aspect of the complex cellular response to this treatment was a progressive lowering of the influx rate of AMD and, consequently, of its endocellular concentration, leading to a late resurgence of transcription. Overall protein synthesis decreased in AMD-treated cells, but more of the residual protein was exported to the cell surface, a fact associated with the development of numerous strands of endoplasmic reticulum and Golgi bodies in the cytoplasm. The lowering of AMD influx during the treatment was not simply due to the decay of protein synthesis, and there was no evidence for a carrier-mediated transport of the drug. It was paralleled by, but seemingly not related to, modifications in cellular microtubules and microfilaments. The rate of AMD influx was restored to levels comparable to those of untreated cells by short exposure to ethylenediaminetetraacetic acid and trypsin. It is concluded that the changes in plasma membrane of 37 RC cells, creating an obstacle to the influx of AMD after long treatment with this drug, probably consist of an accumulation and/or a different distribution of glycoproteins or other surface components on the cell surface.