Inhibition of endogenous murine retrovirus expression by L-beta-3,4-dihydroxyphenylalanine (L-dopa) methyl ester

Induction of endogenous xenotropic type-C virus from Kirsten sarcoma-virus-transformed BALB/c (K-BALB) mouse cells was inhibited by short-term exposure to L-beta-3,4-dihydroxyphenylalanine (L-dopa) methyl ester. Partially synchronized cells cultured for 1-4 h with 0.8-1.6 mM L-dopa methyl ester and subsequently induced with 5-iododeoxyuridine (IdUrd), cycloheximide and histidinol showed inhibition of virus activation. Incorporation of thymidine, uridine and leucine was measured at the end of the drug treatment and during the subsequent induction period. L-dopa methyl ester had a pronounced effect on DNA synthesis, reducing it by more than 85% during a 4-h incubation period, whereas RNA and protein synthesis remained largely unaffected. Removal of the drug and replacement with fresh medium did not reverse DNA synthesis or virus activation during the subsequent induction interval. L-dopa methyl ester was also shown to potentially function as an analogue of tyrosine in this cell system. These results suggest that inhibition of virus induction may be caused by inhibiting the normal progressing of cells through the S phase of the cell cycle.