experiment. The remaining 2 monkeys will remain alive for long-term neurological 
assessment and virologic follow-up. 
D. Optimization Studies: 
1. Ganciclovir Dose Optimization 
The optimization of ganciclovir dosage was evaluated in the rat 9L brain 
tumor model. The purpose of the experiment was to determine the minimal dose of 
GCV necessary to completely eradicate the tumor. 9L cells, pre-transduced with the 
HS-tk gene and selected in I.Omg/ml G418, were used for tumor inoculation. 
Ganciclovir was given IP at doses of 10, 20, and 30 mg/Kg/day for 6 days. 
The animals were sacrificed 3 days following cessation of ganciclovir. In 
vivo fixation of the brain was achieved with intracardiac infusion of 4% formaldehyde 
solution. The brains were removed and with the use of the surgical microscope, the 
tumors were dissected free of the surrounding brain and weighed. Tumors in the 
ganciclovir-treated groups shrank to a mean weight of less than 10% of the tumors in 
the untreated control rats and were composed of necrotic non-viable cells. There was 
no significant difference between the three GCV dosages (Figure 4). Thus, tumor 
regression was obtained with GCV doses routinely applied to man. 
[794] 
Recombinant DNA Research, Volume 15 
