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ARTICLE |

An Evaluation of the Carcinogenicity of Simian Virus 40 in Man FREE

Joseph F. Fraumeni, Jr., MD; Fred Ederer, MA; Robert W. Miller, MD, DrPH
[+] Author Affiliations

Bethesda, Md.

Medical Officer (Dr. Fraumeni) and Chief (Dr. Miller), Epidemiology Branch, and Head, Biometrics Analysis Section, Biometry Branch (Mr. Ederer), National Cancer Institute, National Institutes of Health, US Public Health Service.


JAMA. 1963;185(9):713-718. doi:10.1001/jama.1963.03060090045016
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THE DISCOVERY that simian virus 40 (SV40) is oncogenic for certain newborn laboratory animals has raised the question of its carcinogenicity in man, particularly since this agent has been found in poliomyelitis and adenovirus vaccines. It is estimated that live SV40 has been injected into and ingested by hundreds of thousands, if not millions, of vaccines.1 Although clinical disease has not been reported, SV40 has low infectivity in man when administered by mouth with attenuated poliovirus vaccine1 and by the respiratory route.2 From the evidence presently available, however, it appears that the largest source of potential human infectivity by SV40 in the US was formalinized poliomyelitis vaccine containing the simian agent administered subcutaneously.3 The purpose of this report is to present a brief review of the literature and an epidemiologic study bearing on this problem.

Review of Literature  In 1960 Sweet and Hilleman4 reported the

REFERENCES

Melnick, J.L., and Stinebaugh, S.:  Excretion of Vacuolating SV40 Virus (Papova Virus Group) After Ingestion as Contaminant of Oral Poliovaccine , Proc Soc Exp Biol Med 109:965-968 ( (April) ) 1962;.
Morris, J.A., et al:  Clinical and Serologic Responses in Volunteers Given Vacuolating Virus (SV40) by Respiratory Route , Proc Soc Exp Biol Med 108:56-59 ( (Oct) ) 1961;.
Goffe, A.P.; Hale, J.; and Gardner, P.S.:  Poliomyelitis Vaccines , Lancet 1:612 ( (March 18) ) 1961;.
Sweet, B.H., and Hilleman, M.R.:  Vacuolating Virus, S.V.40 , Proc Soc Exp Biol Med 105:420-427 ( (Nov) ) 1960;.
Gerber, P.; Hottle, G.A.; and Grubbs, R.E.:  Inactivation of Vacuolating Virus (SV40) by Formaldehyde , Proc Soc Exp Biol Med 108:205-209 ( (Oct) ) 1961;.
Meyer, H.M., Jr., et al:  Studies on Simian Virus 40 , J Immun 88:796-806 ( (June) ) 1962;.
Magrath, D.I.; Russell, K.; and Tobin, J.O'H.:  Vacuolating Agent , Brit Med J 1:287-288 ( (July 29) ) 1961;.
Eddy, B.E., et al:  Tumors Induced in Hamsters by Injection of Rhesus Monkey Kidney Cell Extracts , Proc Soc Exp Biol Med 107:191-197 ( (May) ) 1961;.
Eddy, B.E., et al:  Identification of Oncogenic Substance in Rhesus Monkey Kidney Cell Cultures as Simian Virus 40 , Virology 17:65-75 ( (May) ) 1962;.
Eddy, B.E.:  Tumors Produced in Hamsters by SV40 , Fed Proc 21:930-935 ( (Nov) -Dec) 1962;.
Girardi, A.J., et al:  Development of Tumors in Hamsters Inoculated in Neonatal Period with Vacuolating Virus, SV40 , Proc Soc Exp Biol Med 109:649-660 ( (March) ) 1962;.
Kirschstein, R.L., and Gerber, P.:  Ependymomas Produced After Intracerebral Inoculation of SV40 into New-born Hamsters , Nature (London) 195:299-300 ( (July 21) ) 1962;.
Rabson, A.S., et al:  Papillary Ependymomas Produced in Rattus (Mastomys) Natalensis Inoculated with Vacuolating Virus (SV40) , J Nat Cancer Inst 29:765-787 ( (Oct) ) 1962;.
Eddy, B.E.; Grubbs, G.E.; and Young, R.D.:  Persistent Infection of Human Carcinoma and Primary Chick Embryo Cell Cultures with Simian Virus 40 , Proc Soc Exp Biol Med 111:718-722 ( (Dec) ) 1962;.
Girardi, A.; Sweet, B.H.; and Hilleman, M.R.:  Factors Influencing Tumor Induction in Hamsters by Vacuolating Virus, SV40 , Proc Soc Exp Biol Med 112:662-667 ( (March) ) 1963;.
Rabson, A.S., and Kirschstein, R.L.:  Induction of Malignancy in vitro in Newborn Hamster Kidney Tissue Infected with Simian Vacuolating Virus (SV40) , Proc Soc Exp Biol Med 111:323-328 ( (Nov) ) 1962;.
Black, P.H., and Rowe, W.P.:  Transformation in Hamster Kidney Monolayers by Vacuolating Virus, SV-40 , Virology 19:107-109 ( (Jan) ) 1963;.
Shein, H.M., et al:  Transformation Induced by Simian Virus 40 in Newborn Syrian Hamster Renal Cell Cultures , Proc Nat Acad Sci USA 49:28-34 ( (Jan) ) 1963;.
Eddy, B.E., et al:  Influence of Route of Injection, Age and Animal Passage on Induction of Neoplasms in Hamsters by Simian Virus 40 , Abstract, International Congress for Microbiology (Montreal) 8:89 ( (Aug) ) 1962;.
Ashkenazi, A., and Melnick, J.L.:  Induced Latent Infection of Monkeys with Vacuolating SV-40 Papova Virus: Virus in Kidneys and Urine , Proc Soc Exp Biol- Med 111: 367-372 ( (Nov) ) 1962;.
Sabin, A.B.: In Second International Conference on Live Poliovirus Vaccines , Pan American Health Organization and World Health Organization, Washington, D.C., 1960;, pp 87-88.
 Field Evidence of Safety, Topic II(B) : In Second International Conference on Live Poliovirus Vaccines , Pan American Health Organization and World Health Organization, Washington, D.C., 1960;, pp 113-227.
Shein, H.M., and Enders, J.F.:  Transformation Induced by Simian Virus 40 in Human Renal Cell Cultures: I. Morphology and Growth Characteristics , Proc Nat Acad Sci USA 48:1164-1172 ( (July) ) 1962;.
Koprowski, H., et al:  Transformation of Cultures of Human Tissue Infected with Simian Virus SV40 , J Cell Comp Physiol 59:281-292 ( (June) ) 1962;.
Rabson, A.S., et al:  Simian Vacuolating Virus (SV40) Infection in Cell Cultures Derived from Adult Human Thyroid Tissue , J Nat Cancer Inst 29:1123-1145 ( (Dec) ) 1962;.
Melnick, J.L.:  Papova Virus Group , Science 135:1128-1130 ( (March 30) ) 1962;.
Francis, T., Jr., et al:  Evaluation of 1954 Poliovaccine Trials: Summary Report , Amer J Public Health 14:1-50 (May, Pt (2) ) 1955;.
Sirken, M.G., and Brenner, B.: Population Characteristics and Participation in Poliomyelitis Vaccination Program, Public Health Monograph No. 61, Washington, D.C.: US Government Printing Office, 1960.
National Office of Vital Statistics, Vital Statistics of the United States; Annual Reports, 1950-1959, Washington, D.C.: US Government Printing Office.
U. S. Bureau of the Census, United States Census of Population; Detailed Characteristics, 1950 and 1960, Washington, D.C.: US Government Printing Office.
U. S. Bureau of the Census, Current Population Reports; Population Estimates, Series P-25, No. 229, Washington, D.C.: US Government Printing Office, May 22, 1961.
Smith, K.O., and Melnick, J.L.:  Method for Staining Virus Particles and Identifying their Nucleic Acid Type in Electron Microscope , Virology 17:480-490 ( (July) ) 1962;.

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Melnick, J.L., and Stinebaugh, S.:  Excretion of Vacuolating SV40 Virus (Papova Virus Group) After Ingestion as Contaminant of Oral Poliovaccine , Proc Soc Exp Biol Med 109:965-968 ( (April) ) 1962;.
Morris, J.A., et al:  Clinical and Serologic Responses in Volunteers Given Vacuolating Virus (SV40) by Respiratory Route , Proc Soc Exp Biol Med 108:56-59 ( (Oct) ) 1961;.
Goffe, A.P.; Hale, J.; and Gardner, P.S.:  Poliomyelitis Vaccines , Lancet 1:612 ( (March 18) ) 1961;.
Sweet, B.H., and Hilleman, M.R.:  Vacuolating Virus, S.V.40 , Proc Soc Exp Biol Med 105:420-427 ( (Nov) ) 1960;.
Gerber, P.; Hottle, G.A.; and Grubbs, R.E.:  Inactivation of Vacuolating Virus (SV40) by Formaldehyde , Proc Soc Exp Biol Med 108:205-209 ( (Oct) ) 1961;.
Meyer, H.M., Jr., et al:  Studies on Simian Virus 40 , J Immun 88:796-806 ( (June) ) 1962;.
Magrath, D.I.; Russell, K.; and Tobin, J.O'H.:  Vacuolating Agent , Brit Med J 1:287-288 ( (July 29) ) 1961;.
Eddy, B.E., et al:  Tumors Induced in Hamsters by Injection of Rhesus Monkey Kidney Cell Extracts , Proc Soc Exp Biol Med 107:191-197 ( (May) ) 1961;.
Eddy, B.E., et al:  Identification of Oncogenic Substance in Rhesus Monkey Kidney Cell Cultures as Simian Virus 40 , Virology 17:65-75 ( (May) ) 1962;.
Eddy, B.E.:  Tumors Produced in Hamsters by SV40 , Fed Proc 21:930-935 ( (Nov) -Dec) 1962;.
Girardi, A.J., et al:  Development of Tumors in Hamsters Inoculated in Neonatal Period with Vacuolating Virus, SV40 , Proc Soc Exp Biol Med 109:649-660 ( (March) ) 1962;.
Kirschstein, R.L., and Gerber, P.:  Ependymomas Produced After Intracerebral Inoculation of SV40 into New-born Hamsters , Nature (London) 195:299-300 ( (July 21) ) 1962;.
Rabson, A.S., et al:  Papillary Ependymomas Produced in Rattus (Mastomys) Natalensis Inoculated with Vacuolating Virus (SV40) , J Nat Cancer Inst 29:765-787 ( (Oct) ) 1962;.
Eddy, B.E.; Grubbs, G.E.; and Young, R.D.:  Persistent Infection of Human Carcinoma and Primary Chick Embryo Cell Cultures with Simian Virus 40 , Proc Soc Exp Biol Med 111:718-722 ( (Dec) ) 1962;.
Girardi, A.; Sweet, B.H.; and Hilleman, M.R.:  Factors Influencing Tumor Induction in Hamsters by Vacuolating Virus, SV40 , Proc Soc Exp Biol Med 112:662-667 ( (March) ) 1963;.
Rabson, A.S., and Kirschstein, R.L.:  Induction of Malignancy in vitro in Newborn Hamster Kidney Tissue Infected with Simian Vacuolating Virus (SV40) , Proc Soc Exp Biol Med 111:323-328 ( (Nov) ) 1962;.
Black, P.H., and Rowe, W.P.:  Transformation in Hamster Kidney Monolayers by Vacuolating Virus, SV-40 , Virology 19:107-109 ( (Jan) ) 1963;.
Shein, H.M., et al:  Transformation Induced by Simian Virus 40 in Newborn Syrian Hamster Renal Cell Cultures , Proc Nat Acad Sci USA 49:28-34 ( (Jan) ) 1963;.
Eddy, B.E., et al:  Influence of Route of Injection, Age and Animal Passage on Induction of Neoplasms in Hamsters by Simian Virus 40 , Abstract, International Congress for Microbiology (Montreal) 8:89 ( (Aug) ) 1962;.
Ashkenazi, A., and Melnick, J.L.:  Induced Latent Infection of Monkeys with Vacuolating SV-40 Papova Virus: Virus in Kidneys and Urine , Proc Soc Exp Biol- Med 111: 367-372 ( (Nov) ) 1962;.
Sabin, A.B.: In Second International Conference on Live Poliovirus Vaccines , Pan American Health Organization and World Health Organization, Washington, D.C., 1960;, pp 87-88.
 Field Evidence of Safety, Topic II(B) : In Second International Conference on Live Poliovirus Vaccines , Pan American Health Organization and World Health Organization, Washington, D.C., 1960;, pp 113-227.
Shein, H.M., and Enders, J.F.:  Transformation Induced by Simian Virus 40 in Human Renal Cell Cultures: I. Morphology and Growth Characteristics , Proc Nat Acad Sci USA 48:1164-1172 ( (July) ) 1962;.
Koprowski, H., et al:  Transformation of Cultures of Human Tissue Infected with Simian Virus SV40 , J Cell Comp Physiol 59:281-292 ( (June) ) 1962;.
Rabson, A.S., et al:  Simian Vacuolating Virus (SV40) Infection in Cell Cultures Derived from Adult Human Thyroid Tissue , J Nat Cancer Inst 29:1123-1145 ( (Dec) ) 1962;.
Melnick, J.L.:  Papova Virus Group , Science 135:1128-1130 ( (March 30) ) 1962;.
Francis, T., Jr., et al:  Evaluation of 1954 Poliovaccine Trials: Summary Report , Amer J Public Health 14:1-50 (May, Pt (2) ) 1955;.
Sirken, M.G., and Brenner, B.: Population Characteristics and Participation in Poliomyelitis Vaccination Program, Public Health Monograph No. 61, Washington, D.C.: US Government Printing Office, 1960.
National Office of Vital Statistics, Vital Statistics of the United States; Annual Reports, 1950-1959, Washington, D.C.: US Government Printing Office.
U. S. Bureau of the Census, United States Census of Population; Detailed Characteristics, 1950 and 1960, Washington, D.C.: US Government Printing Office.
U. S. Bureau of the Census, Current Population Reports; Population Estimates, Series P-25, No. 229, Washington, D.C.: US Government Printing Office, May 22, 1961.
Smith, K.O., and Melnick, J.L.:  Method for Staining Virus Particles and Identifying their Nucleic Acid Type in Electron Microscope , Virology 17:480-490 ( (July) ) 1962;.
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