Changes in the Ribonucleoproteins of the Nucleolus following Inhibition of Synthesis of Deoxyribonucleic Acid

Abstract

BY means of an improved toluidine blue–molybdate staining procedure¹ two types of ribonucleoprotein (RNP) can be very clearly demonstrated in the nucleolus. One type is the pars amorpha and the other consists of minute granules or hollow spheres and appears to correspond to the nucleolini of classical cytologists². Enlargement of the nucleolini has been observed in cells infected with viruses and in cells in which the onset of mitosis is blocked by large doses of colchicine³. The relationship between the changes in the nucleolini and nucleic acid metabolism is not clear in these systems. An examination of the nucleolar RNP was therefore undertaken in cells treated with 5-fluorodeoxyuridine (FUDR) since the metabolic changes produced by this antimetabolite have been extensively studied. FUDR inhibits synthesis of deoxyribonucleic acid (DNA) by blocking the formation of thymidylic acid^4,5. When cells in tissue culture are treated with FUDR, DNA synthesis is prevented, cell division is arrested and the metabolism of ribonucleic acid (RNA) is disturbed^6,7. During one generation time of HeLa cells, the DNA per cell remains constant, the cytoplasmic RNP doubles and the nuclear RNP is unchanged. Salzman and Sebring provide evidence that the effect of FUDR on RNA metabolism of HeLa cells is mediated through its effect on DNA synthesis since the process is reversed by thymidine, but not by uridine⁷.