The therapeutic effect of herpes simplex virus thymi-dine kinase/ganciclovir (HSV-tk/GCV) system on hepa-tocellular carcinoma was studied in this experimeflt. Thetk-containing retroviral recombinants were used to infecthepatoma cells (BEL-7402) and the cells were treated withganciclovir (0-1000 pg/ml). The results showed that HSV-tk gene could be efficielltly transferred in Vitro into hep-atoma cells and stably expressed. The growth potentialof the tk-containing cells was significantly inhibited byGCV (P<0.01) as compared to the non-tk-containing cells.The antitumor effect of HSV-tk/GCV system was also pro-duced ex vivo in tk-containing tumor of nude mice as char-acterized by a marked decrease in tumor growth after GCVtreatment contrary to a progressive enlargement of non-tk-containing tumors. Although the histological examinationdemonstrated that the efficiency of the gene transfer wasless than 30%, the killing effect of HSV-tk/GCV systemon hepatocellular carcinoma was still significantIy gener-ated. The proper mechanism of HSV-tk gene therapy onhepatic tumor referred as "bystander effect" in therapeu-tic approach has not been found in this study and requiredto be explored further.
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