The fluorinated pyrimidines are used in the treatment of cancer in man. The inhibition of the thymidylate synthetase step is a major site of action of these compounds. However, the "activated" derivatives of fluorouracil and fluorouridine have been shown to cause the inhibition of rRNA maturation. The proposed project is designed to determine the role that the inhibition of RNA metabolism has in the cytotoxic action of these compounds. In understanding the relative importance of the effects on RNA, Novikoff hepatoma cell lines which are sensitive and resistant to fluorouracil and fluorodeoxyuridine will be used. The metabolic pathways for the "activation" of these compounds will be studied in the two cell lines.