Association of 2',3'-dideoxyinosine metabolites with the mitochondrial compartment in a human leukemic cell line (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

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Association of 2',3'-dideoxyinosine metabolites with the mitochondrial compartment in a human leukemic cell line (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A2671 1994. Unique Identifier : AIDSLINE ICDB/95604356
Vazquez-Padua MA; Gonzalez MT; Retrovirus Research Center, Universidad Central del Caribe,; School of Medicine, Bayamon, PR 00960

Abstract: 2',3'-dideoxyinosine (DDI) is an anti-Human Immunodeficiency Virus drug used in the treatment of AIDS patients. In spite of its potent antiviral activity, DDI shows significant toxicity in the clinic. It has been proposed that effects on mitochondrial (mt) DNA may play a role in the toxicity of DDI and other antiviral drugs. We examined the intracellular flux of DDI and its various metabolites to the mt population of U937 cells, a human leukemic cell line. After a 24 hr exposure to 10 uM 3H-DDI, subcellular fractionation of U937 cells showed less than 2.5% of the total radioactivity associated with the mt fraction. However, very low levels of DDI-derived radioactivity could be detected in the fractions corresponding to mtDNA and mtRNA. Upon further analysis it was found that about 90% of the radioactivity was associated with the detergent-soluble fraction of mt extracts from the same cells. On the other hand, significant amounts of radioactivity were found associated with nuclear DNA and RNA. We are currently evaluating the possibility of detecting DDI-derived metabolites in mtDNA upon chronic treatment of U937 cells with DDI.
Keywords: Cell Fractionation Didanosine/METABOLISM/*PHARMACOLOGY DNA, Mitochondrial/*DRUG EFFECTS Human Leukemia/*PATHOLOGY Mitochondria/METABOLISM Tumor Cells, Cultured ABSTRACTKWDcellfractionationdidanosine/metabolism/KWDpharmacologydna,mitochondrial/KWDdrugeffectshumanleukemia/KWDpathologymitochondria/metabolismtumorcells,culturedabstract
950330
M9530843

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