V Survival 
received on day 1 kbalb-STK cells. Both groups received GCV on day 5 for 5 doses 
(figure 22). Another experiment used the SKOV-3 tumor cell line as the day 1 
inoculum. Mice injected on day 0 with kbalb-LNL tumor cells either received no further 
cells or 2 x 10 6 SKOV-3 (Group 1) or 2 x 10 6 SKOV-3-STK tumor cells on day 1 with 
GCV therapy beginning on day 4 for 7 doses (Group 2)(figure 23). Group 2 was the 
only group of mice with a preexisting tumor burden to have long term survivors in any 
experiment. It also appears that injection of xenogeneic tumor cells does not affect 
tumor growth of a preexisting murine tumor. 
22 
The ability of GCV to kill irradiated HSV-TK expressing tumor cells was analyzed. 
The kbalb-LNL or kbalb-STK tumor cells were exposed to 3,000 rads and then 
cultured in vitro. The cells were exposed to 50 uM GCV at varying times post- 
irradiation ranging from no GCV (Group C) to GCV added on day 0, day 2, day 4, or 
day 6 post irradiation (Group 0, 2, 4, and 6 respectively). The irradiated kblab-LNL 
tumor cells exposed to GCV continued to remain metabolically active as evidenced by 
their ability to remain attached to a tissue culture dish up to 28 days post irradiation ( 
the left column of Table I represents the days on which the irradiated cells were 
observed for metabolically active cells). The attached cells were qualitatively scored; 
++++ indicates approximately 90-100% of the plate is covered by cells, +++ indicates 
50-90% of the dish is covered, ++ indicates 10-50% of the dish is covered, + indicates 
<10% of the dish covered with cells, and - indicates <1% covered with cells. We 
determined that GCV had virtually no affect on irradiated TK negative cells. Irradiated 
TK positive cells exposed to GCV on day 0 died within a week, while cells exposed to 
GCV after day 0 died after approximately one month (Table I). 
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Recombinant DNA Research, Volume 15 
[585] 
