Summary
Certain bacteriophages have been found in live, virus vaccines, while a few others have been associated with disease states. Some of these phages have produced abnormal growth of eukaryotic tissue cultures. For this reason bacteriophages ϕX-174, MS2, T2 and an isolate from live virus vaccines, ϕV-1, were incubated with human cell cultures for examination of chromosomal effects, cell proliferation and viability. Mitogen-stimulated lymphocytes and human embryonic kidney tissue cultures showed no increase in chromosomal abnormalities for high doses of phage-infected versus control cultures. Tritiated-thymidine uptake, correlated with mitotic indices for phage-treated lymphocyte culture, indicated a reduction in cell division, while 51-chromium release studies showed no cell death occurring in these cultures. This suggested that inhibition of DNA synthesis was occurring in some cells. The presence of phage in the supernate of cells that were exposed to phage suggested the possibility of phage attachment to the plasma membranes of lymphocytes, which may in turn affect the suppression of DNA synthesis.
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Merril, C. R., T. B. Friedman, A. F. Attallah, M. R. Geier, K. Krell, and R. Yarkin. 1972. Isolation of bacteriophages from commercial sera. In Vitro 8: 91–93.
Chu, F. C., J. B. Johnson, H. C. Orr, P. G. Probst, and J. C. Petricciani. 1973. Bacterial virus contamination of fetal bovine sera. In Vitro 9: 31–34.
Petricciani, J. C., F. C. Chu and J. B. Johnson. 1973. Bacteriophages in live virus vaccines. Proc. Soc. Exp. Biol. Med. 144: 789–792.
Moody, E. E. M., M. D. Trousdale, J. H. Jorgensen, and A. Shelokov. 1975. Bacteriophages and endotoxin in licensed live-virus vaccines. J. Infect. Dis. 131: 588–591.
Netter, R., R. J. P. LeGo, J. L. Menetrat, J. F. Viev, J. L. Malarbet, and B. Klein. 1975. Bacteriophage control of some virus vaccines and organ extracts for human use. J. Biol. Stand. 3: 311–319.
Montes, L. F., C. A. Phillips, S. H. Black, and M. E. McBride. 1966. Electron microscopic evidence for a bacteriophage cycle in diptheroids observed in human skin. J. Invest. Dermatol. 47: 466–474.
Mankiewicz, E. 1965. Bacteriophages that lyse mycobacteria and corynebacteria, and show cytopathogenic effects on tissue cultures of renal cells ofCeroopithecus aethiops. Can. Med. Assoc. J. 92: 31–33.
Petricciani, J. C., B. C. Meyer, R. J. Vallancourt, and W. J. Duryea. 1975. Preliminary attempts to detect interactions between coliphages and two attenuated vaccine viruses. J. Biol. Stand. 3: 335–340.
Orr, H. C., P. G. Probst, D. C. Littlejohn, F. C. Chu, and J. C. Petricciani. 1974. Persistence of bacteriophage in experimentally infected cell cultures. Appl. Microbiol. 27: 1105–1107.
Uhr, J. W., M. S. Finkelstein, and J. B. Bauman. 1962. Antibody formation. III. The primary and secondary antibody response to bacteriophage ϕX-174 in guinea pigs. J. Exp. Med. 115: 655–670.
Milstein, J. B., J. C. Petricciani, and J. R. Walker. 1975. Proceedings of the 75th Meeting of the American Society for Microbiology. H68.
Merril, C. R., M. R. Geier, and J. C. Petricciani. 1971. Bacterial virus gene expression in human cells. Nature 233: 398–400.
Geier, M. R., and C. R. Merril. 1972. Lambda phage transcription in human fibroblasts. Virology 47: 638–643.
Jones, R. H., A. Rowan, J. W. Foster, and F. W. Bennett. 1965. Evidence for growth ofStreptococcus cremoris bacteriophage in embryonating eggs and persistence in tissue cultures. J. Dairy Sci. 48: 782.
Leavitt, J. C., L. M. Schechtman, P. O. P. Ts'o, E. Borenfreund, and A. Bendich. 1976. The attachment and penetration of T7 DNA/phage in Syrian hamster embryonic cells. Biochem. Biophys. Acta 435: 167–183.
Kolata, G. B. 1975. Phage in live virus vaccines: Are they harmful to people? Science 187: 522–523.
Adams, M. H. 1950. Methods of study of bacterial viruses. In: J. H. Comroe, Jr. (Ed.),Methods in Medical Research. Vol. 2. The Year Book Publishers, Inc., Chicago, pp. 7–8.
Furuse, K., and I. Watanabe. 1971. Effects of ultraviolet light (UV) irradiation on RNA phage in H2O and D2O. Virology 46: 171–172.
Hancock, V. K., and E. K. Knott. 1935. Irradiated blood transfusion in treatment of infections. Physiotherapy Rev. 15: 22–26.
Rabinowitz, Y. 1964. Separation of lymphocytes, polymorphonuclear leukocytes and monocytes on glass columns, including tissue culture observations. Blood 23: 811–828.
Moorhead, P. S., P. C. Nowell, W. J. Mellman, D. M. Battips, and D. A. Hungerford. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20: 613–616.
Turner, J. H., and D. L. Hutchinson. 1974. Cyclohexylamine mutagenicity: Anin vivo evaluation utilizing fetal lambs. Mutat. Res. 26: 407–412.
Wigzell, H. 1965. Quantitative titrations of mouse H-2 antibodies using Cr51-labelled target cells. Transplantation 3: 423–431.
Rogentine, G. N., Jr., and B. A. Plocinik. 1967. Application of the51Cr cytotoxicity technique to the analysis of human lymphocyte isoantigens. Transplantation 5: 1323–1333.
Kabat, E. A., and M. M. Mayer. 1961.Experimental Immunochemistry. Thomas. Springfield, Ill., p. 149.
Smith, S. R., D. B. Thomas, and A. C. Riches. 1972. Metaphase accumulation in tumour isografts following the administration of colcemid, vinblastine or vincristine. J. Anat. 111: 480.
Lehman, E. L. 1959.Testing Statistical Hypotheses. John Wiley and Sons, Inc., New York, pp. 140–143.
Hancock, V. H., and E. K. Knott. 1934. Irradiated blood transfusion in treatment of infections. Northwest Med. 33: 200–204.
Wenger, S. L., K. Wasserloos, S. Jingeleski, and J. H. Turner. Attachment of bacteriophages to lymphocyte plasma membranes, manuscript in preparation.
Notani, N., and S. H. Goodgal. 1966. On the nature of recombinants formed during transformation ofHemophilus influenzae. J. Gen. Physiol. 49 (Suppl.): 197–209.
Bodmer, W. F. 1972. DNA synthesis and transformation ofBacillus subtilis. In: L. Ledoux (Ed.),Uptake of Informative Molecules by Living Cells. North-Holland Publishing Co., Amsterdam, pp. 122–29.
Stone, A. B. 1970. General inhibition ofEscherichia coli macromolecular synthesis of high multiplicities of bacteriophage ØX-174. J. Mol. Biol. 47: 215–229.
Nichols, W. W. 1970. Virus-induced chromosome abnormalities. In: C. Clifton (Ed.),Annual Review of Microbiology. Vol. 24. Annual Reviews, Inc., Palo Alto, Calif., pp. 479–500.
Trump, B. F., and A. U. Arstila. 1971. Cell injury and cell death. In: M. F. LaVia, and R. B. Hill, Jr. (Eds.),Principles of Pathology. Oxford University Press, New York, p. 85.
Marx, J. L. 1976. Cell biology: Cell surfaces and the regulation of mitosis. Science 192: 455–457.
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This work was supported by HEW/FDA Grant No. 223-73-1171.
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Wenger, S.L., Turner, J.H. & Petricciani, J.C. The cytogenetic, proliferative and viability effects of four bacteriophages on human lymphocytes. In Vitro 14, 543–549 (1978). https://doi.org/10.1007/BF02616097
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DOI: https://doi.org/10.1007/BF02616097