Effect of thiopyrimidine ribonucleosides on DNA and RNA synthesis in synchronized mammalian cell cultures

• Published in: Experimental cell research Vol. 69; no. 2; pp. 377 - 383
• Main Author: Lozzio, Carmen B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.1971
• Subjects: Animals; Autoradiography; Cell Line; Cell Nucleus - metabolism; Cells, Cultured - metabolism; Colchicine - pharmacology; Cricetinae; Cytoplasm - metabolism; DNA - biosynthesis; Mitosis - drug effects; RNA - biosynthesis; Thiouridine - pharmacology; Thymidine - metabolism; Time Factors; Tritium; Uridine - metabolism
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/0014-4827(71)90238-2

The uptake of 3H-uridine into RNA and of 3H-thymidine into DNA was investigated in synchronized Chinese hamster cells which had been exposed to thiopyrimidine ribonucleosides. The cells were synchronized at metaphase by reversal of colcemid inhibition; these cells were then labeled with either 3H-thymidine or 3H-uridine at selected times, and analyzed in autoradiographs. Incorporation of 3H-thymidine into DNA was not inhibited by administration to the cells of 2-thiouridine or 4-thiouridine (4 × 10 −3 M). Exposure of the cells to the anti-metabolites for over 15 h significantly reduced the incorporation of 3H-uridine into nuclear RNA and completely blocked the labeling of cytoplasmic RNA. This finding is interpreted as an indication that RNA synthesis was inhibited in cells which continued to synthesize DNA. The inhibition of RNA synthesis hindered cell division and decreased cell viability. This lethal effect is similar to the “unbalanced growth” induced by inhibitors of DNA synthesis. The thiopyrimidine ribonucleosides, however, killed mammalian cells without inhibiting DNA synthesis.