Oligonucleotide degradation contributes to resistance to antisense compounds.
A subline of the human B cell lymphoma DHL-4, grown in the artificial serum-free medium HB101, displayed a resistant phenotype to the activity of an antisense oligodeoxynucleotide (aODN) effective on the parental DHL-4 line. It was found that the cellular uptake of the 18mer aODN in the two cell lines was almost the same. In contrast, the unresponsive subline DHL-4r degraded the aODN very efficiently, in contrast to the stability of aODN inside cells of the parental DHL-4 line. Activation of the degrading 'machinery' combined with selective properties of the artificial medium may be responsible for the loss of responsiveness to aODN.
Ryte
A
A
Department of Pharmacology, University of Milan, Italy.
Morelli
S
S
Mazzei
M
M
Alama
A
A
Franco
P
P
Canti
G F
GF
Nicolin
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D004351:Drug Resistance; D006801:Humans; D016393:Lymphoma, B-Cell; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000032:analysis / Q000494:pharmacology*; D010761:Phosphorus Radioisotopes; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D010761:Phosphorus Radioisotopes