Antisense oligodeoxynucleoside methylphosphonate inhibition of mouse c-myc p65 protein expression in E mu-c-myc transgenic mice.
In transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (E mu-myc), it was found that methylphosphonates do not induce acute toxicity following intravenous administration of a 300 nmol dose. In addition, recovery of methylphosphonates from the blood plasma of treated mice indicated that the oligomers remained intact up to 3 hours, while their concentrations decreased rapidly for the first hour, then slowly decreased over the next two hours. Finally, methylphosphonate oligomers targeted against c-myc mRNA inhibited production of c-myc p65 protein in peripheral and splenic lymphocytes, relative to a scrambled sequence oligomer, 4 hours after injection of a 300 nmol dose, as indicated by immunofluorescence of fixed cells stained with an anti-c-myc antiserum.
Wickstrom
E
E
Department of Chemistry, University of South Florida, Tampa 33620.
Bacon
T A
TA
Wickstrom
E L
EL
Werking
C M
CM
Palmiter
R D
RD
Brinster
R L
RL
Sandgren
E P
EP
D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects; D005803:Genes, Immunoglobulin; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D016376:Oligonucleotides, Antisense; D063065:Organophosphonates; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger