ATP‐resistant variants of transformed mouse fibroblasts

Abstract

Addition of ATP to cultures of transformed mouse fibroblasts, 3T6 cells, resulted in cell growth inhibition, whereas the growth of the non-transformed counterparts, 3T3 cells, was only slightly affected. The inhibition was found to be specific for adenine nucleotides, and concentration dependent. At relatively low concentrations (e.g., 1.0 mM) the effect of ATP was cytostatic, whereas at higher concentrations (e.g., 1.0 mM) a cytotoxic effect was exerted. ATP-resistant variants of 3T6 cells were selected by exposure of cultures to gradually elevated concentrations of ATP. The variants were found to resemble the non-transformed counterparts, 3T3 cells, more than the 3T6 parent cells, by the following criteria: ATP-induced alterations in the membrane potential, changes in membrane permeability, cell growth inhibition, and colony formation on soft agar. The data indicate that long exposure of the transformed cells to external ATP results in redifferentiation and reduction in their tumorigenicity.

Growth inhibition of lung cancer cells by adenosine 5′‐triphosphate

“…Activation of P2X 7 receptors further results in formation of non-selective pores, which induces an increase in nonselective membrane permeability for aqueous solutes that ordinarily do not cross the cell membrane [Chiozzi et al, 1996;Dubyak and el-Moatassim, 1993;Macino et al, 1996]. These effects have been seen in many transformed cells [Belzer and Friedberg, 1989;Chahwala and Cantley, 1984;Fang et al, 1992;Rapaport, 1983;Rapaport et al, 1983;Spungin and Friedberg, 1993;Vandewalle et al, 1994] but not in untransformed cells [Di Virgilio et al, 1989;Hatta et al, 1994;Kitagawa et al, 1988;Rozengurt et al, 1977;Weisman et al, 1984].…”

“…Box 616, 6200 MD Maastricht, The Netherlands. E-mail: Dagnelie@epid.unimaas.nl concentration below 50 mM [Huang et al, 1991;Wang et al, 1992], whereas higher ATP concentrations inhibited growth [Belzer and Friedberg, 1989;Chahwala and Cantley, 1984;Fang et al, 1992;Hatta et al, 1994;Rapaport, 1983;Rapaport et al, 1983;Seetulsingh-Goorah and Stewart, 1998;Spungin and Friedberg, 1993;Vandewalle et al, 1994]. These effects were not observed in untransformed control cells [Hatta et al, 1993[Hatta et al, , 1994Kitagawa et al, 1988;Mure et al, 1992;Rapaport, 1983].…”