Combination studies with 3′-azido-3′-deoxythymidine (AZT) plus ICI D1694: Cytotoxic and biochemical effects

摘要: Abstract The cytotoxicity of 3′-azido-3′-deoxythymidine (AZT), a thymidine analogue, and ICI D1694, folate-based thymidylate synthase (TS) inhibitor, was examined individually in combination two human tumor cell lines, MGH-U1 bladder cancer HCT-8 colon cells, grown as monolayer culture with without (TdR). In addition, TS inhibition, [ 3 H]AZT incorporation into DNA, H]AZT-MP (monophosphate) production, DNA double-strand breaks were measured. Twenty-four hour exposure AZT at 0.5, 5, 50 500 μM not cytotoxic to or cells colony-forming assay. D1694 increased drug concentration, the ic 90 , respectively, 0.0064 0.01 0.009 0.018 cells. TdR concentrations 0.1 1.0 did affect either line. kill. for 0.0037 0.0075 combined D1694. 0.015 plus increasing Concentrations producing an by 319 569% MHG-U1, 243 400% formation paralleled increase incorporated DNA. AZT, caused breaks, these agents being additive. CFU-GM survival, exposed concentrations, those used revealed that therapeutic index greater than alone. These findings suggest may antitumor effect minimal myelosuppression. We conclude increases