UPTAKE, INTRACELLULAR-DISTRIBUTION, AND STABILITY OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE BY SCHISTOSOMA-MANSONI

Citation
Lf. Tao et al., UPTAKE, INTRACELLULAR-DISTRIBUTION, AND STABILITY OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE BY SCHISTOSOMA-MANSONI, Antisense research and development, 5(2), 1995, pp. 123-129
Citations number
29
Categorie Soggetti
Medicine, Research & Experimental","Biothechnology & Applied Migrobiology
ISSN journal
10505261
Volume
5
Issue
2
Year of publication
1995
Pages
123 - 129
Database
ISI
SICI code
1050-5261(1995)5:2<123:UIASOO>2.0.ZU;2-R
Abstract
The in vitro uptake, cellular distribution, efflux, stability, and tox icity levels of an oligodeoxynucleotide phosphorothioate (PS-oligonucl eotide) have been studied in mature Schistosoma mansoni worms. The int racellular accumulation of S-35-labeled PS-oligonucleotide occurred ro ughly in proportion to the worm body mass over a wide concentration ra nge, whether the worms were exposed singly or in mating pairs. Cellula r uptake was dependent on the extracellular concentration. A minor fra ction (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%) fracti ons. 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 showe d that PS-oligonucleotide was digested slowly. Efflux of the oligonucl eotide was time and temperature dependent. Significant toxicity to the cultured worms did not occur until tile PS-oligonucleotide concentrat ion was over 8 mg/ml (1 mM).