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Nature of Transient Inhibition of Deoxyribonucleic Acid Synthesis in HeLa Cells by Parainfluenza Virus 1 (Sendai)

Israel Institute for Biological Research, Ness Ziona, and School of Medicine, Tel Aviv University, Ramat Aviv, Israel

ABSTRACT

Adsorption of ultraviolet-inactivated Sendai virus, at high or low multiplicity, to HeLa cells caused a transient increased incorporation of ³H-thymidine into the cellular deoxyribonucleic acid (DNA). In HeLa cells synchronized by a double-thymidine block, this increased incorporation of thymidine during the S phase lasted from about 30 to 90 min after virus adsorption. The observations that the kinetics of accumulation of radioactive thymidine in the nucleotide pool did not differ in control and in the virus-treated cells and that the ³²P incorporation into the DNA of the virus-treated cells was inhibited at the same time indicate that the augmented incorporation of ³H-thymidine into DNA results from a transient block in the endogenous pathway of thymidine synthesis. Chromatographic analysis of the nucleotide pool of the virus-treated cells labeled with ¹⁴C-formate indicates that methylation of deoxyuridine monophosphate to thymidine monophosphate is inhibited. It is suggested that the inhibition is caused by a block of either the thymidilate synthetase or some step in the tetrahydrofolate cycle.

¹ This work is part of a Ph.D. thesis to be submitted to the Tel Aviv University by P. Fuchs.