AEGiS-07IAC: A pre-clinical in vitro toxicological model using human lymphocytes.

7th International AIDS Conference


Florence, Italy — June 16-21, 1991

Print this Article


A pre-clinical in vitro toxicological model using human lymphocytes.

Int Conf AIDS 1991 Jun 16-21; 7:100 (abstract no. M.A.1034)
Foster BC, Wilson DL, Tryphonas H, Whitehouse LW, Khan SR; Health & Welfare Canada, Health Protection Branch, Ottawa, Ontario, Canada

OBJECTIVE: The purpose of this study was to determine whether transformed and peripheral blood leukocytes could be used in a pre-clinical in vitro lymphocyte proliferation assay (3H-thymidine uptake) to determine the potential toxicity of AIDS drugs and whether there would be drug interactions.

METHODS: Epstein-Barr virus transformed and freshly isolated peripheral blood leukocytes isolated from HIV-1 seronegative donors were incubated in RPMI 1640 media with fetal bovine serum and Conconavalin A in 96 well flat bottom plates. ZDV alone and in combination with diclazuril (DC), fluconazole (FC), itraconazole (IC) and ketoconazole (KC) was added at t-0. 3H-thymidine was added at 72 hr. Cells were harvested at 96 hr and counted for uptake of radiolabel. Statistical significance was assigned using Student's T test.

RESULTS: ZDV had a linear dose response on reducing the uptake of 3H-thymidine. IC and KC in combination with ZDV significantly reduced 3H-thymidine uptake compared to that observed with either IC or KC alone. DC and FC had no apparent toxicity and did not alter the toxicity observed with ZDV, whereas IC and KC may contribute to the toxicity of ZDV.

CONCLUSIONS: The results obtained in this study are consistent with clinical findings that IC and KC are highly toxic to leukocytes. This assay may provide an inexpensive, rapid model to determine the pre-clinical toxicity of drugs alone and in combination.

Keywords: AEGIS, Zidovudine, Lymphocytes, Anti-HIV Agents, HIV-1, Thymidine, Evaluation Studies, HIV-1 Reverse Transcriptase, Herpesvirus 4, Human, Animal, Cattle, Human, In Vitro, ICA7KWDaegis,zidovudine,lymphocytes,anti-hivagents,hiv-1,thymidine,evaluationstudies,hiv-1reversetranscriptase,herpesvirus4,human,animal,cattle,human,invitro,ica7
910616
MA1034

Copyright © 1991 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.