The influence of phosphorothioate oligodeoxynucleotides on various organs in vivo.
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.
Nieborowska-Skórska
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Białek
A P
AP
Nicolaides
N C
NC
Iozzo
R V
RV
Kawalec
M
M
Calabretta
B
B
Kawiak
J
J
Marlicz
K
K
Skórski
T
T
D000818:Animals; D001752:Blast Crisis / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013873:Thionucleotides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides