Comparison of mitochondrial morphology, mitochondrial DNA content, and cell viability in cultured cells treated with three anti-human immunodeficiency virus dideoxynucleosides.
The toxic effects of various concentrations of 2',3'-dideoxycytidine (ddC), 2',3'-dideoxy-2',3'-didehydrothymidine (D4T), and 2',3'-dideoxyinosine (ddI) on CEM cells after 4 days of culture were assessed by measuring cell viability, mitochondrial DNA (mtDNA) content, and mitochondrial morphology. Cell viability and mtDNA content in drug-treated cultures were significantly reduced in a concentration-dependent fashion in comparison with cell viability and mtDNA content in untreated cultures. Cells in the treated cultures also showed significant changes in their mitochondrial morphologies which included distortion and reduction of the cristae and numerous vesicles. Unique features of the morphological changes were associated with each drug. The decrease in cell viability and mtDNA content and the increase in mitochondrial ultrastructural changes were directly related to the concentrations of the drugs used. The potencies of these compounds in reducing cell viability, mtDNA content, and normal mitochondria were in the order ddC > D4T > ddI. Comparison of the three assays used demonstrated that mtDNA content is a significantly more sensitive measure of drug toxicity than cell viability and mitochondrial morphology for the three compounds studied.
Medina
D J
DJ
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520.
Tsai
C H
CH
Hsiung
G D
GD
Cheng
Y C
YC
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000032:analysis*; D016049:Didanosine / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D018119:Stavudine / Q000633:toxicity*; D016047:Zalcitabine / Q000633:toxicity*
D004272:DNA, Mitochondrial; D016047:Zalcitabine; D018119:Stavudine; D016049:Didanosine