3'-Azido-2',3'-dideoxythymidine (AZT) preferentially incorporates into liver mitochondrial DNA of CD-1 mice dosed with AZT in drinking water for 28 days (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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3'-Azido-2',3'-dideoxythymidine (AZT) preferentially incorporates into liver mitochondrial DNA of CD-1 mice dosed with AZT in drinking water for 28 days (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A2113 1995. Unique Identifier : AIDSLINE ICDB/95609888
Olivero OA; Fullerton NF; Beland FA; Poirier MC; NCI, NIH, Bethesda, MD 20892-4255

Abstract: Liver mitochondrial DNA is a target for toxicity of some nucleoside analog drugs including 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodouracil (5-FIAU). AZT, the thymidine nucleoside analog used in the therapy of AIDS (acquired immunodeficiency syndrome), has been reported to be hepatotoxic. We have examined AZT incorporation into liver mitochondrial (mt) and genomic (g) DNA of mice given 0, 180, 360 and 720 ug AZT/ml in the drinking water for 28 days. Hepatic nuclear and mitochondrial fractions were separated by differential centrifugation. DNA was prepared from each fraction and assayed by a radioimmunoassay for AZT. Incorporation of AZT into gDNA was not detectable (greater than 0.1 pmol AZT/ug DNA) at any dose. Values for incorporation of AZT into mtDNA were 0.26 +/- 0.09, 0.43 +/- 0.09 and 0.48 +/- 0.25 pm AZT/ug DNA (mean +/- sd; n=4) in livers of mice given 180, 360 and 720 ug AZT/ml water respectively. Therefore, the preferential incorporation of AZT into mtDNA may contribute to the hepatotoxicity of AZT.
Keywords: Animal *DNA Damage DNA, Mitochondrial/*DRUG EFFECTS/METABOLISM Mice Mitochondria, Liver/*DRUG EFFECTS/METABOLISM Zidovudine/*PHARMACOLOGY/PHARMACOKINETICS ABSTRACTKWDanimalKWDdnadamagedna,mitochondrial/KWDdrugeffects/metabolismmicemitochondria,liver/KWDdrugeffects/metabolismzidovudine/KWDpharmacology/pharmacokineticsabstract
950930
M9591323

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