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
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).