COMPARISON OF MITOCHONDRIAL MORPHOLOGY, MITOCHONDRIAL-DNA CONTENT, AND CELL VIABILITY IN CULTURED-CELLS TREATED WITH 3 ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS DEOXYNUCLEOSIDES

The toxic effects of various concentrations of 2',3'-dideoxycytidine ( ddC), 2',3'-dideoxy-2',3'-didehydrothymidine (D4T), and 2',3'-dideoxyi nosine (ddI) on CEM cells after 4 days of culture were assessed by mea suring cell viability, mitochondrial DNA (mtDNA) content, and mitochon drial morphology. Cell viability and mtDNA content in drug-treated cul tures were significantly reduced in a concentration-dependent fashion in comparison with cell viability and mtDNA content in untreated cultu res. Cells in the treated cultures also showed significant changes in their mitochondrial morphologies which included distortion and reducti on of the cristae and numerous vesicles. Unique features of the morpho logical changes were associated with each drug. The decrease in cell v iability and mtDNA content and the increase in mitochondrial ultrastru ctural changes were directly related to the concentrations of the drug s used. The potencies of these compounds in reducing cell viability, m tDNA content, and normal mitochondria were in the order ddC > D4T > dd I. 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 .