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.
The influence of phosphorothioate oligodeoxynucleotides on various organs in vivo / Nieborowska Skórska, M; Białek, AP; Nicolaides, NC; Iozzo, RV; Kawalec, M; CALABRETTA, Bruno; Kawiak, J; Marlicz, K; Skórski, T.. - In: FOLIA HISTOCHEMICA ET CYTOBIOLOGICA. - ISSN 0239-8508. - STAMPA. - 34:(1996), pp. 69-73.
The influence of phosphorothioate oligodeoxynucleotides on various organs in vivo.
CALABRETTA, Bruno;
1996
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.
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