Comparison of drug effects on RNA tumor viruses and on transformed cells.

Attempts to develop in vitro methods to test inhibitors for replication of C-type RNA tumor virus are made at two levels of the life cycle of the virus: 1) Formation of the proviral DNA, and 2) transcription and processing of viral RNA. Compounds such as rifamycin derivatives were found to be effective in interfering with the first process and compounds such as cordycepin, a nucleoside analogue, blocked effectively the second process. On the other hand, a class of known anti-tumor agents, glucocorticoids, was found to stimulate (10 fold or more) the induction of C-type virus following 5-iodo-2'-deoxyuride (IDU) treatment of murine cells. This is an intriguing example of a multi-focal action of an anti-tumor agent. We are exploring the implication of this for relapse or retransformation following successful chemotherapy in leukemic mice. Attempts are being made to develop an in vitro animal cell model for quantitative cytotoxic assays for compounds active in the above system and for comparing their effects on both normal and virus transformed cells.