Antisense oligodeoxynucleoside methylphosphonate inhibition of mouse c-myc p65 protein expression in E mu-c-myc transgenic mice

Nucleic Acids Symp Ser. 1991:(24):151-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Enhancer Elements, Genetic
  • Gene Expression / drug effects
  • Genes, Immunoglobulin
  • Genes, myc* / drug effects
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology*
  • Organophosphonates / pharmacology
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Messenger / genetics

Substances

  • Oligonucleotides, Antisense
  • Organophosphonates
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger