Inhibitory effect of halogenated pyrimidines on multiplication of viruses in tissue culture systems.

It is of interest to examine the inhibitory effect of halogenated pyrimidines on the multiplication of viruses in tissue culture systems, in view of finding the fundamental knowledge to obtain antiviral drugs. Concerning the inhibition of biosynthesis of nucleic acid by halogenated pyrimidines, Heiderberg and his coworkers(') found that 5-fluorouracil inhibited the process of biosynthesis of RNA and DNA in mammalian tumor cells (1957). Since then, a lot of reports(2) have been published as to the inhibitory effect of these derivatives on the synthesis of nucleic acid in microorganisms, intact animals, tumor bearing animals, cultivated cells and so on. From these reports, it was suggested that 5-fluoro uracil and other halogenated pyrimidines should inhibit not only the growth of mammalian tumor but the incorporation of precursors into DNA-thymine and RNA-uracil in bacteria and bacteriophages, and the inhibition of 5-fluorode oxyuridine on DNA synthesis in animals and microorganisms should be due to the blocking the conversion of deoxyuridylic acid to thymidylic acid and the formation of abnormal nucleic acid in which a halogenated pyrimidine was incorporated. On the basis of the findings above, Salzman(3) found that 5-fluorodeoxyuridine markedly inhibited the multiplication of vaccinia virus, one of DNA containing viruses, in HeLa cells but was ineffective on the growth of polio virus, one of RNA containing viruses. From these results, it was suggested by him that 5-fluorodeoxyuridine might be useful to distinguish whether some virus should belong to DNA containing virus or to RNA containing virus. This report describes that these compounds did not show any effect on adeno virus, though this virus belongs to the categoly of DNA containing virus. On the contrary, Ginsberg(4), Simmon(5) and Green(6) have reported that 5-fluorodeoxyuridine exerted the inhibitory effect on the virus. In order to confirm how the antiviral spectrum