1. The influence of phosphorothioate oligodeoxynucleotides on various organs in vivo
- Author
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Nieborowska-Skórska M, Ap, Białek, Nicholas Nicolaides, Rv, Iozzo, Kawalec M, Calabretta B, Kawiak J, Marlicz K, and Skórski T
- Subjects
Male ,Mice ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Tumor Cells, Cultured ,Animals ,Humans ,Tissue Distribution ,Mice, SCID ,Oligonucleotides, Antisense ,Thionucleotides ,Blast Crisis ,Oligonucleotides Antisense/pharmacology ,Thionucleotides/pharmacokinetics ,Neoplasm Transplantation - Abstract
To characterize the distribution and toxicity of phosphorothioate antisense oligodeoxynucleotides ([S]ODNs) in vivo, the mice, previously injected with BV173 leukemic cells (Philadelphia chromosome-positive chronic myeloid leukemia blast-crisis), received intravenously 26-mer BCR-ABL antisense oligodeoxynucleotides (1 mg/mouse/day) for 9 consecutive days. Our investigation revealed that [S]ODNs were distributed to almost all organs except the brain with the highest level in the liver, spleen and kidneys. They were also detected in CD10+ leukemic cells isolated from spleen and bone marrow. Intracellular distribution assay showed the presence of [S]ODNs most prominently in nuclear and cytoplasmic fractions. Our data demonstrated no significant toxicity of [S]ODNs except the increase in spleen weight.
- Published
- 1996