Adenoviral delivery of recombinant DNA into transgenic mice bearing hepatocellular carcinomas

ABSTRACT To evaluate the applicability of recombinant adenoviral vectors in gene transfer to liver cancers, we infused the recombinant adenoviruses AD5CMV-LacZ and Ad5CMV-p53 through the portal veins into two lines of transgenic mice, one bearing the SV40 T antigen and the other the human hepatitis B viral envelope protein. These transgenic animals develop hepatocellular carcinomas (HCC) with predictable pathological manifestations. The levels of expression of the transgenes were dependent upon the viral doses. In all cases, high levels of expression were detected within 2 or 3 days after infusion, but were drastically reduced 7 days after infusion. Significant toxicities were found in the infused animals: >80% of them died within 7 days after infusion with 1010 pfu, and transgenic animals bearing HCC apparently were more sensitive to viral toxicity. Although a lower dose (109 pfu/animal) produced less toxicity, the levels of expression were substantially reduced (only about 10% of that in animals infused...