Effect of Cytosine Arabinoside on the Replication of the Moloney Sarcoma Virus in 3T3 Cell Cultures

• Published in: JNCI : Journal of the National Cancer Institute 1969-03, Vol.42 (3), p.399-411
• Main Authors: Hirschman, Shalom Z., Fischinger, Peter J., Zaccari, Joseph J., O'Connor, Timothy E.
• Format: Article
• Language: English
• Subjects: Animals; Clone Cells - growth & development; Culture Techniques; Cytarabine - antagonists & inhibitors; Cytarabine - pharmacology; Cytosine Nucleotides - pharmacology; DNA - antagonists & inhibitors; DNA - biosynthesis; DNA, Viral - biosynthesis; Mice; Moloney murine leukemia virus; RNA - biosynthesis; RNA, Viral - biosynthesis; Thymidine; Time Factors; Uridine; Virus Replication - drug effects
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/42.3.399

Cytosine arabinoside inhibited DNA synthesis, measured by incorporation of thymidine into DNA, in 3T3 cell cultures, but did not affect RNA synthesis, as measured by the incorporation of uridine into RNA. When added to 3T3 cell cultures, cytosine arabinoside inhibited the growth of Moloney murine sarcoma virus (MSV). MSV-infected 3T3 cell cultures treated with either 10−3 M, 10−4 M, or 10−5 M cytosine arabinoside during the first 16 hours of virus growth yielded no detectable virus at 48 hours of incubation. However, some virus was recoverable after 7 days' incubation of the infected 3T3 cell cultures. The inhibition of DNA synthesis in 3T3 cell cultures by cytosine arabinoside was reversed by deoxycytidine; 10−3 M deoxycytidine canceled the effects of 10−5 M cytosine arabinoside both on growth of 3T3 cells and the replication of MSV. The first 48 hours of the growth curve of MSV in 3T3 cell cultures could be closely duplicated by the addition of cytosine arabinoside for 16 hours at various periods during the first 48 hours of viral growth, and measurement of the titer of MSV at 48 hours. It is concluded that MSV depends on DNA synthesis for successful replication in 3T3 cell cultures.