title: Action of deoxycoformycin on human T cell colonies in vitro.
abstract: The potent adenosine deaminase inhibitor, deoxycoformycin (dCF), is currently under evaluation in the treatment of lymphoid malignancy. We show that dCF inhibits the growth in soft agar of T cell colonies from PHA stimulated human peripheral blood lymphocytes. In contrast to previous attempts to develop an in vitro model for analysis of the drug's action, concentrations lower than 10(-9)M are effective, and no 'priming' by pharmacological concentrations of adenosine is required. Maximum inhibition is obtained when dCF is present over the first 4 hr of cellular exposure to PHA. T cells already proliferating in response to PHA are less sensitive to dCF, implying that S-phase events are not primary targets of the drug's action. Colony inhibition does not appear to be due to alteration in the production of, or sensitivity to, soluble T cell growth factors. In suspension cultures, dCF at concentrations up to 10(-5)M fails to inhibit early PHA-induced volume changes, or later mitosis, in peripheral blood lymphocytes. The results show that there is a critical dCF sensitive step early in PHA stimulation. It involves those T cells capable of forming colonies and may be conditioned by the cellular microenvironment.
mesh_terms: D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003470:Culture Media; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D015649:Pentostatin; D010835:Phytohemagglutinins / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
chemical_list: D003470:Culture Media; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin