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Laboratory of Molecular Oncology, Inserm U186, and CNRS URA 0156, Institut Pasteur de Lille, F59019 Lille Cedex, France [T. D., J-M. V., J. J. C., N. D., J. R.], and Laboratory of Biophysics and Radiobiology, Université Libre de Bruxelles, B1640 Rhode-St. Genèse, Belgium [J. J. C., J. R.]
The formation of tumors in adult nude mice from transformed human mammary epithelial cells was drastically inhibited (>80%) both after coinjection of tumoral cells and virus or after a single s.c. injection of parvovirus H-1 at the site of cell implantation prior to tumor formation. Moreover, when injected i.v. in animals bearing preformed tumors, H-1 virus was able to slow down and even in some cases to revert neoplastic growth. Thus, H-1 virus achieved the suppression of implanted tumors of human origin under conditions where the immune antitumor mechanisms of the recipient animals were dramatically impaired. Viral infection was not accompanied by detectable deleterious side effects. Imprints of H-1 virus DNA were found in one residual tumor. Normal human mammary epithelial cells were also compared with homologous transformed cells, either derived from tumors (three lines) or containing simian virus 40 (one line), for their susceptibility to the lytic replication of H-1 virus in vitro. Transformed cell lines were more sensitive to virus-induced killing than secondary cultures of normal cells. Moreover, the former had much greater abilities than the latter to amplify viral DNA and to express the viral nonstructural protein NS-1. Altogether, these results are compatible with the idea that the oncosuppressive activity exerted by H-1 virus may be mediated, at least in part, by virus replication in developing tumors.
1 This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Association pour la Recherche sur le Cancer, Institut Pasteur de Lille (France), the Ministère de la Politique Scientifique, Caisse Générale d'Epargne et de Retraite, and Fonds National de la Recherche Scientifique (Belgium). T. D. and J-M. V. are supported by the Institut Pasteur de Lille and the Ministère de l'Industrie et de la Recherche, respectively.
2 To whom requests for reprints should be addressed.
Received 11/14/88. Revised 3/13/89. Accepted 3/21/89.
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