Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates.
Cancer Res
; 52(24): 6741-5, 1992 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-1458461
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Linfócitos
/
Regulação da Expressão Gênica
/
DNA Antissenso
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Proteínas Proto-Oncogênicas c-myc
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article