Differential inhibition of mitogen induced T cell proliferation by 5-azacytidine and cytosine-arabinoside.
The cytotoxic drugs 5-azacytidine and cytosine-arabinoside influence the enzymatic methylation of DNA in opposite ways (1,2). The in vitro effects of these two drugs on Con A induced proliferation of thymic and splenic rat lymphocytes were investigated. Cytosine-arabinoside was found to inhibit mitogen induced proliferation already at a concentration of 0.001 microM, whereas 5-azacytidine was inhibitory only above concentrations of 1 microM. A stimulation of mitogen induced T cell proliferation was consistently seen with 5-azacytidine, but not with cytosine-arabinoside, at concentrations lower than the cytotoxic concentration. The results show that 5-azacytidine and cytosine-arabinoside interfere with mitogen stimulated lymphocyte proliferation by different mechanisms and suggest that hypomethylated DNA plays a role in the proliferation of T cells.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008745:Methylation; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology
D003561:Cytarabine; D003208:Concanavalin A; D004247:DNA; D001374:Azacitidine