IN-VIVO ADENOVIRAL-MEDIATED HUMAN P53 TUMOR-SUPPRESSOR GENE-TRANSFER AND EXPRESSION IN RAT-LIVER AFTER RESECTION

Background. The aim of this study was to establish a clinically releva nt model for gene transfer to gene products in the treatment of primar y and metastatic liver tumors. Methods. Full-size or 50% hepatectomize d rat livers were subjected to asanguineous portal perfusion with a re plication-defective adenoviral vector encoding wild-type p53 (Ad5p53), whereas control animals received adenoviral vector encoding Escherich ia coli beta-galactosidase (beta-gal) (Ad5LacZ) or Ringer's lactate on ly. Liver biopsy specimens, blood samples, and liver weight were DNA/R NA polymerase chain reaction, (PCR) and Western blots for p53 and beta -gal. Liver integrity was assessed by histologic findings, serum trans aminase levels, and synthetic function. Results. The gene transfer rat e in whole liver and after hepatectomy ranged from 20% to 40%. DNA PCR showed Ad sequences in livers transduced with Ad5p53 and Ad5LacZ. RNA PCR and Western blot confirmed expression and production of recombina nt wild-type p53. Liver regeneration teas not affected by p53 gene tra nsduction. Liver histologic findings and synthetic Junction were not d ifferent between transduced and control groups. Conclusions. Ad5p53 ge ne transfer to full-size or hepatectomized livers is efficient. river tumor-suppressor transduction of the liver is a safe and promising adj uvant in cancer gene therapy.