Skip to main content
PMC home page
Applied Microbiology logoLink to Applied Microbiology
. 1965 Jul;13(4):579–589. doi: 10.1128/am.13.4.579-589.1965

In Vivo Antiviral Activity of 1,3-Bis(2-Chloroethyl)-1-Nitrosourea

Robert W Sidwell 1, Glen J Dixon 1, Sara M Sellers 1, Frank M Schabel Jr 1
PMCID: PMC1058301  PMID: 14339266

Abstract

A prolongation in the lives of Swiss mice inoculated intracerebrally with lymphocytic choriomeningitis virus (LCM) was observed after treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A variety of treatment schedules, including therapy once or twice daily up to 17 days and single treatments at various times after virus inoculation, were employed. Virus titers ranging to greater than 104 were detected in the blood and brains of surviving drug-treated animals. In three comparative studies in which different treatment schedules were used, BCNU was shown to exert a protective effect approximately equal to that of methotrexate in LCM virus-infected mice. Tests were also carried out to investigate the activity of BCNU in mice experimentally infected with eastern equine encephalomyelitis (EEE) virus, western equine encephalomyelitis virus, Semliki Forest (SF) virus, herpes simplex virus, influenza virus strain PR8, vaccinia virus strain WR, Rous sarcoma virus, Friend leukemia virus (FLV), and poliovirus. Slight increases in life span were observed in the treated EEE, SF, and influenza PR8 virus-infected animals. Significant reduction in splenomegaly in FLV-infected animals treated with BCNU was demonstrated. The possible mechanisms of LCM virus inhibition by BCNU, on the basis of these and other studies, were postulated to be either specific antiviral activity or inhibition of “lethal” immune response to the LCM virus. Each of these postulates is discussed.

Full text

PDF
588

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BERENBAUM M. C. The effect of cytotoxic agents on the production of antibody to T.A.B. vaccine in the mouse. Biochem Pharmacol. 1962 Jan;11:29–44. doi: 10.1016/0006-2952(62)90088-6. [DOI] [PubMed] [Google Scholar]
  2. BRYAN W. R., MOLONEY J. B., CALNAN D. Stable standard preparations of the Rous sarcoma virus preserved by freezing and storage at low temperatures. J Natl Cancer Inst. 1954 Oct;15(2):315–329. [PubMed] [Google Scholar]
  3. CHIRIGOS M. A., MOLONEY J. B., HUMPHREYS S. R., MANTEL N., GOLDIN A. Response of a virus-induced murine lymphoid leukemia to drug therapy. Cancer Res. 1961 Jul;21:803–811. [PubMed] [Google Scholar]
  4. CHIRIGOS M. A., RAUSCHER F. J., KAMEL I. A., FANNING G. R., GOLDIN A. Studies with the murine leukemogenic Rauscher virus. I. Chemotherapy studies with in vivo and in vitro assay systems. Cancer Res. 1963 Jun;23:762–769. [PubMed] [Google Scholar]
  5. CHIRIGOS M. A. STUDIES WITH THE MURINE LEUKEMOGENIC RAUSCHER VIRUS. 3. AN IN VIVO ASSAY FOR ANTI-VIRAL AGENTS. Cancer Res. 1964 Jul;24:1035–1041. [PubMed] [Google Scholar]
  6. EAGLE H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med. 1955 Nov 1;102(5):595–600. doi: 10.1084/jem.102.5.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. ELSON L. A., GALTON D. A., TILL M. The action of chlorambucil (CB. 1348) and busulphan (myleran) on the haemopoietic organs of the rat. Br J Haematol. 1958 Oct;4(4):355–374. doi: 10.1111/j.1365-2141.1958.tb06038.x. [DOI] [PubMed] [Google Scholar]
  8. FURUSAWA E., CUTTING W., FURST A. Inhibitory effect of antiviral compounds on viruses in vivo and in mouse ascites cells in vitro. Proc Soc Exp Biol Med. 1963 Mar;112:617–622. doi: 10.3181/00379727-112-28120. [DOI] [PubMed] [Google Scholar]
  9. HAAS V. H., BRIGGS G. M., STEWART S. E. Inapparent lymphocytic choriomeningitis infection in folic acid-deficient mice. Science. 1957 Aug 30;126(3270):405–406. doi: 10.1126/science.126.3270.405-a. [DOI] [PubMed] [Google Scholar]
  10. HAAS V. H., STEWART S. E., BRIGGS G. M. Folic acid deficiency and the sparing of mice infected with the virus of lymphocytic choriomeningitis. Virology. 1957 Feb;3(1):15–21. doi: 10.1016/0042-6822(57)90020-x. [DOI] [PubMed] [Google Scholar]
  11. HAAS V. H., STEWART S. E. Sparing effect of A-methopterin and guanazolo in mice infected with virus of lymphocytic choriomeningitis. Virology. 1956 Aug;2(4):511–516. doi: 10.1016/0042-6822(56)90007-1. [DOI] [PubMed] [Google Scholar]
  12. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  13. HUMPHREYS S. R., GLYNN J. P., GOLDIN A. Suppression of the homograft response by pretreatment with antitumor agents. Transplantation. 1963 Jan;1:65–69. doi: 10.1097/00007890-196301010-00008. [DOI] [PubMed] [Google Scholar]
  14. LERNER E. M., 2nd, HAAS V. H. Histopathology of lymphocytic choriomeningitis in mice spared by amethopterin. Proc Soc Exp Biol Med. 1958 Jun;98(2):395–399. doi: 10.3181/00379727-98-24055. [DOI] [PubMed] [Google Scholar]
  15. LEVY H. B., HAAS V. H. Alteration of the course of lymphocytic choriomeningitis in mice by certain antimetabolites. Virology. 1958 Jun;5(3):401–407. doi: 10.1016/0042-6822(58)90035-7. [DOI] [PubMed] [Google Scholar]
  16. ROWE W. P. Protective effect of pre-irradiation on lymphocytic choriomeningitis infection in mice. Proc Soc Exp Biol Med. 1956 May;92(1):194–198. doi: 10.3181/00379727-92-22425. [DOI] [PubMed] [Google Scholar]
  17. SCHABEL F. M., Jr, JOHNSTON T. P., McCALEB G. S., MONTGOMERY J. A., LASTER W. R., SKIPPER H. E. Experimental evaluation of potential anticancer agents VIII. Effects of certain nitrosoureas on intracerebral L1210 leukemia. Cancer Res. 1963 Jun;23:725–733. [PubMed] [Google Scholar]
  18. SUGIURA K. The effect of antibiotics on a spectrum of tumors. Antibiot Annu. 1959;7:924–942. [PubMed] [Google Scholar]
  19. WARWICK G. P. THE MECHANISM OF ACTION OF ALKYLATING AGENTS. Cancer Res. 1963 Sep;23:1315–1333. [PubMed] [Google Scholar]
  20. WHEELER G. P., BOWDON B. J., HERREN T. C. DISTRIBUTION OF C14 FROM C14-LABELED 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA (NSC-409962) IN TISSUES OF MICE AND HAMSTERS AFTER INTRAPERITONEAL ADMINISTRATION OF THE AGENT. Cancer Chemother Rep. 1964 Nov;42:9–12. [PubMed] [Google Scholar]
  21. WHEELER G. P. Studies related to the mechanisms of action of cytotoxic alkylating agents: a review. Cancer Res. 1962 Jul;22:651–688. [PubMed] [Google Scholar]

Articles from Applied Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES