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Effects of Protease Inhibitors on Chemical Induction of Type C Virus¹

Biological Carcinogenesis Program, Frederick Cancer Research Center, Frederick, Maryland 21701

A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virustransformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, -N-tosyl-L-lysine chloromethyl ketone, and two naturally occurring oligopeptide inhibitors, antipain and leupeptin, were found to inhibit induction of virus by cycloheximide and histidinol. Virus activation by 5-iododeoxyuridine was inhibited to a lesser degree. During the time cells were exposed to these compounds, there was little inhibition of [³H]uridine incorporation into total cellular RNA or polyadenylic acid cytoplasmic messenger RNA, suggesting that inhibition of proteolysis, and not RNA transcription, was responsible for blocking virus induction.

¹ This work was supported by Contract N01-CO-75380 with the National Cancer Institute, NIH, Bethesda, Md. 20205.

² To whom requests for reprints should be addressed, at Frederick Cancer Research Center, P.O. Box B, Building 560, Frederick, Md. 21701.

Received 11/17/78. Accepted 4/26/79.