Purine nucleoside-dependent inhibition of cellular proliferation in 1321N1human astrocytoma cells

We examined the effects of purines and the pyrimidine UTP on cellular proli feration in the human astrocytoma cell line 1321N1. Treatment of cultured c ells with 100 muM ATP or 2-chloroadenosine (2-CA) resulted in significant r eductions in cell numbers after 2 days, whereas adenosine (ADO) exhibited a slower time course of inhibition of cell growth. Treatment with 100 muM UT P nad no effect on cell numbers. 2-Chloroadenosine but neither ATP nor ADO resulted in an increase in cell death rates. A significant portion of the i nhibitory response to ATP, ADO, or 2-CA was sensitive to the purine nucleos ide transport inhibitor S-(p-nitrobenzyl)-6-thioguanosine, suggesting that uptake into cells was required for the inhibitory response. At least the ma jority of the observed responses to purines was not mediated by P1 (adenosi ne) receptors, because effects of ATP, ADO, or 2-CA were not affected by tr eatment of cells with the P1 receptor antagonist 8-(p-sulfophenyl)-theophyl line. The absence of any known P2 (nucleotide) receptors in 1321N1 cells, c oupled with the failure of the relatively stable ATP analog adenosine 5'-O- (3-thiotriphosphate) to alter cell growth rates, suggests that ATP acts ind irectly to inhibit proliferation via one or more metabolic products. Althou gh intracellular effects of purine nucleosides should be taken into account in future studies using 1321N1 cells, our findings also suggest 1321N1 cel ls as an excellent model for intracellular actions of nucleosides.