PREVENTION OF TUMOR-FORMATION IN A MOUSE MODEL OF BURKITTS-LYMPHOMA BY 6 WEEKS OF TREATMENT WITH ANTI-C-MYC DNA PHOSPHOROTHIOATE

Background: Transgenic mice bearing a murine immunoglobulin enhancer/c -myc fusion transgene (E mu-myc) provide a useful model for Burkitt's lymphoma. Materials and Methods: Groups of 12 E mu-myc mice were treat ed prophylactically for 6 weeks after weaning with anti-c-myc DNA phos phorothioate (20 mg/kg/day), scrambled control DNA, or saline, deliver ed by microosmotic pumps. Results: Half of the mice treated with salin e or scram bled control DNA displayed palpable tumors by 8-9 weeks aft er birth, and 95% of them did so by 16 weeks, but 75% of the mice trea ted with antisense DNA were still free of tumors at the age of 26 week s. Antisense therapy ablated MYC antigen in the spleens of tumor-beari ng mice. Plasma physiological parameters indicated no acute toxicity. Conclusions: Long-term tumor resistance after anti-c-myc DNA therapy i mplies induction of a host response. Prophylactic anti-c-myc DNA thera py might prevent lymphoma in asymptomatic individuals displaying c-myc translocations.