Prevention of tumor formation in a mouse model of Burkitt's lymphoma by 6 weeks of treatment with anti-c-myc DNA phosphorothioate.
BACKGROUND
Transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc) provide a useful model for Burkitt's lymphoma.


METHODS
Groups of 12 Emu-myc mice were treated prophylactically for 6 weeks after weaning with anti-c-myc DNA phosphorothioate (20 mg/kg/day), scrambled control DNA, or saline, delivered by micro-osmotic pumps.


RESULTS
Half of the mice treated with saline or scrambled control DNA displayed palpable tumors by 8-9 weeks after birth, and 95% of them did so by 16 weeks, but 75% of the mice treated with antisense DNA were still free of tumors at the age of 26 weeks. Antisense therapy ablated MYC antigen in the spleens of tumor-bearing mice. Plasma physiological parameters indicated no acute toxicity.


CONCLUSIONS
Long-term tumor resistance after anti-c-myc DNA therapy implies induction of a host response. Prophylactic anti-c-myc DNA therapy might prevent lymphoma in asymptomatic individuals displaying c-myc translocations.
Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.
Y
Y
Huang
R
R
Snyder
M
M
Kligshteyn
E
E
Wickstrom
D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D015152:Blotting, Northern; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000473:pathology / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D017931:DNA Primers; D016373:DNA, Antisense / Q000494:pharmacology* / Q000633:toxicity; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012964:Sodium / Q000097:blood; D013873:Thionucleotides; D013997:Time Factors
D016588:Anticarcinogenic Agents; D001786:Blood Glucose; D017931:DNA Primers; D016373:DNA, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013873:Thionucleotides; D012964:Sodium; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase