Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates.

Autor: Wickstrom E; Department of Chemistry, University of South Florida, Tampa 33620., Bacon TA, Wickstrom EL
Jazyk: angličtina
Zdroj: Cancer research [Cancer Res] 1992 Dec 15; Vol. 52 (24), pp. 6741-5.
Abstrakt: In transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc), it was found that antisense DNA methylphosphonates targeted against c-myc mRNA inhibited production of c-MYC protein in peripheral lymphocytes. The decrease in protein was measured 3-4 h after i.v. administration of a 300-nmol dose. c-MYC was detected by immunofluorescence of fixed cells stained with an anti-c-MYC antiserum. In addition, DNA methylphosphonates did not induce acute toxicity following i.v. administration of a 300-nmol dose. An identically administered scrambled sequence oligomer did not decrease c-MYC protein or induce toxicity. Finally, recovery of DNA methylphosphonates from the blood plasma of treated mice indicated that the oligomers remained intact up to 3 h, while their concentrations decreased rapidly for the first h, then slowly decreased over the next 2 h. This is the first demonstration of sequence-specific antisense DNA methylphosphonate inhibition of gene expression in the bloodstream of an animal model.
Databáze: MEDLINE