Summary
Normal rat kidney (NRK) cell were found to be resistant to neoplastic transformation by diverse carcinogenic chemicals. To study chemical-retroviral co-carcinogenesis in this cells they were infected with a low multiplicity of Moloney murine leukemia virus (M-MLV). Using a single cell cloning procedure, a virus-producing clone was isolated from the infected cells, which was shown to carry only one integrated M-MLV provirus per cell. It was found that this single provirus was sufficient to render the clone susceptible to transformation by 3-methylcholanthrene (3-MC). However this clone responded differently to the carcinogen at different passages after infection. When exposed to 3-MC at a low passage postinfection (passage 5), cell transformation was evident only after 11 subsequent subcultures. On the other hand when it was chemically treated at a high passage postinfection (passage 29), cell transformation could clearly be detected already at the next subculture after the chemical treatment. It is suggested that an M-MLV-mediated cumulative effect is necessary to complement the action of the carcinogen in order to complete the carcinogenic process in these cells. This cumulative viral effect appeared to be associated with a change in the control of the virus expression, since 3-MC was found to stimulate virus replication in this clone also only at the high passage postinfection. Indeed virus release by cells of isolated transformed foci, produced by the chemical-M-MLV co-carcinogenesis, was extremely higher than by untransformed cells.
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References
Aboud, M., Weiss, O., Salzberg, S.: Rapid quantitation of interferon with chornically oncornavirus-producing cells. Infect. Immun.13, 1626–1632 (1976).
Aboud, M., Shoor, R., Salzberg, S.: Effect of interferon on the uncoating of murine leukemia virus not related to the antiviral state. J. gen. Virol.51, 425–429 (1980).
Brown, R. L., Crossen, P. E.: Increased incidence of sister chromatid exchanges in Rauscher leukemia infected mouse embryo fibroblasts. Exptl. Cell. Res.103, 418–420 (1976).
Huleihel, M., Aboud, M.: Effect of mouse interferon on cell transformation and virus production in rat cells infected with Moloney murine sarcoma and leikemia viruses. Int. J. Cancer29, 471–476 (1982).
Huleihel, M., Aboud, M.: Inhibition of retrovirus DNA supercoiling in interferontreated cells. J. Virol.48, 120–126 (1983).
Jaenisch, R.: Endogenous retroviruses. Cell32, 120–126 (1983).
Kimbal, P. C., Simon, M. C., Mishra, N. K.: Towards a model for the molecular genetics of carcinogenesis in rats. Proc. Natl. Acad. Sci. U.S.A.77, 3450–3454 (1980).
Majone, F., Montaldi, A., Roncheses, F., DeRossi, A., Chieco-Bianchi, L., Lavis, A. G.: Sister chromatid exchanges inducedin vivo andin vitro by chemical carcinogens in mouse lymphocytes carrying endogenized Moloney murine leukemia virus. Carcinogenesis4, 33–37 (1983).
Maniatis, T., Fritsch, E. F., Sambrook, J.: Molecular cloning. A laboratory Manual. Cold Spring Harbor, N. Y.: Cold Spring Harbor Laboratories 1982.
O'Brien, S. J., Bonner, T. I., Cohen, M., O'Connel, C., Nash, W. G.: Mapping of an endogenous retroviral sequence to human chromosome 18. Nature300, 74–77 (1983).
Price, P. J., Suk, W. A., Freeman, A. E.: Type-C RNA tumor viruses as determinants of chemical carcinogenesis: effect of sequence of treatment. Science177, 1003–1004 (1972).
Rabson, A. B., Steel, P. E., Graon, C. F., Martin, M. A.: mRNA transcripts related to full-lengt of endigenous retroviral DNA in human cells. Nature306, 604–607 (1983).
Repaske, R., O'Neill, R. R., Steele, P. E., Martin, M. A.: Characterization and partial nucleotide sequence of endogenous type-C retrovirus segments in human chromosomal DNA. Proc. Natl. Acad. Sci. U.S.A.80, 678–682 (1983).
Rowe, W., Pogh, W. Z., Hartley, J. M.: Plaque assay technique for murine leukemia viruses. Virology42, 1136–1139 (1970).
Tennant, R. W., Rascati, R. J.: Mechanisms of carcinogenesis involving endogenous retroviruses. In:Slaga, T. J. (ed.), Carcinogenesis, Modifiers of Chemical Carcinogenesis, Vol. 5, 185–204. New York: Raven Press 1980.
Tsuchida, R., Rich, M. R.: Chromosomal aberrations in viral leukomogenesis. I. Friend and Rauscher leukemia. J. Natl. Cancer Inst.33, 33–47 (1964).
Varmus, E. H., Shank, P. R.: Unintegrated viral DNA is synthesized in the cytoplasm of avian sarcoma virus transformed duck cells by viral DNA polymerase. J. Virol.18, 567–573 (1976).
Waters, R., Mishra, N., Bouck, N., DiMayorca, G., Regan, J. D.: Partial inhibition of postreplication repair and enhanced frequency of chemical transformation in rat cells. Proc. Natl. Acad. Sci. U.S.A.74, 238–242 (1977).
Weinstein, I. B.: Current concepts on mechanisms of chemical carcinogenesis. Bulletin N.Y. Acad. Med.54, 366–383 (1978).
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Hassan, Y., Huleihel, M., Priel, E. et al. Effect of moloney murine leukemia virus on the carcinogenicity of 3-methylcholanthrene in normal rat kidney cells. Archives of Virology 90, 63–71 (1986). https://doi.org/10.1007/BF01314145
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DOI: https://doi.org/10.1007/BF01314145