Inhibition by acyclovir of herpes simplex virus type 2 morphologically transformed cell growth in tissue culture and tumor‐bearing animals

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Abstract
Rat embryo fibroblasts (REF) morphologically transformed by herpes simplex virus type 2 (HSV‐2) and tumor‐derived cells were tested for ability to grow in the presence of 9‐(2‐hydroxyethoxymethyl) guanine (acyclovir). Results indicated that the effective dose of acyclovir (ACV) required to inhibit HSV‐2‐transformed and tumor‐derived cell growth by 50% (ED50) compared to mock‐treated control cells averaged 15 to 75 μg/ml. In contrast, the ED50 of acyclovir was more than 250 μg/ml for nontransformed REF, retrovirus‐transformed rat cells, and human HEp‐2 cells. HSV‐2‐transformed and tumor‐derived cells after both low (less than 30) and high (greater than 30) serial passages expressed detectable levels of the virus‐coded thymidine kinase (TK) measured in cell extracts by serum neutralization assay. HSV‐2‐transformed or tumor‐derived cells converted two‐ to ten‐fold more acyclovir to phosphorylated forms than nontransformed REF cells. Preliminary data showed that the drug inhibited tumor development in newborn syngeneic rats inoculated with HSV‐2‐transformed cells. The inhibitory activity of acyclovir and presence of low levels of HSV‐2 TK activity appeared to correlate.