Uptake, Intracellular Distribution, and Stability of Oligodeoxynucleotide Phosphorothioate by Schistosoma mansoni

Autor: Waranya Wongwit, Sudhir Agrawal, Kenneth A. Marx, Liang-Feng Tao, Robert M. Coleman, Zhiwei Jiang
Rok vydání: 1995
Předmět:
Zdroj: Antisense Research and Development. 5:123-129
ISSN: 1050-5261
DOI: 10.1089/ard.1995.5.123
Popis: The in vitro uptake, cellular distribution, efflux, stability, and toxicity levels of an oligodeoxynucleotide phosphorothioate (PS-oligonucleotide) have been studied in mature Schistosoma mansoni worms. The intracellular accumulation of 35S-labeled PS-oligonucleotide occurred roughly in proportion to the worm body mass over a wide concentration range, whether the worms were exposed singly or in mating pairs. Cellular uptake was dependent on the extracellular concentration. A minor fraction (13%) of the PS-oligonucleotide taken up by the worm accumulated in the surface tegumental coat. Most of the PS-oligonucleotide taken up localized in the cytosol (54%) and the nuclei-enriched (33%) fractions. In a time course study on adult worms in culture, oligonucleotide uptake was observed within the first 2 h and peaked at about 36 h. A decrease in the intracellular concentration of the PS-oligonucleotide was observed by 42 h. Analysis of the extracted oligonucleotides showed that PS-oligonucleotide was digested slowly. Efflux of the oligonucleotide was time and temperature dependent. Significant toxicity to the cultured worms did not occur until the PS-oligonucleotide concentration was over 8 mg/ml (1 mM).
Databáze: OpenAIRE