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Effects of prolonged treatment with decarbazine on tumour metastatic potential in mice bearing Lewis lung carcinoma

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The effects of decarbazine on tumour growth and metastatic dissemination upon treatment protracted for 10 tumour transplant generations were examined in mice bearing Lewis lung carcinoma. Primary tumour growth is unaffected by the drug, independently from the duration of the treatment. In contrast, dacarbazine significantly inhibits the formation of lung metastasis. The proportion of mice with metastasis decreases for an increasing number of transplant generations of treatment, and after 10 transplant generations of treatment metastatic capacity is completely lost in immunocompetent mice. The reduction in metastatic potential is relatively stable, being retained for three successive transplant generations without treatment. The metastatic potential of treated tumours in immunosuppressed mice is substantially similar to that in immunocompetent hosts, indicating that chemical xenogenization of tumour cells does not occur as reported for transplantable mouse leukaemias. The results obtained using clonally selected tumour lines with different metastatic potential rule out the selection by dacarbazine of tumour cell sublines with reduced metastatic potential as the mechanism of the drug's action. Upon prolonged treatment, dacarbazine appears to cause a rather stable and dramatic loss in metastatic potential, not accompanied by resistance, which might be attributed to genotypic alteration(s) of tumour cells, and which might participate into the clinical effects of the drug.

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Authors and Affiliations

  1. Institute of Pharmacology, Faculty of Pharmacy, University of Trieste, Trieste

    Sonia Zorzet & Sabrina Pacor

  2. Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy

    Laura Perissin, Valentina Rapozzi & Tullio Giraldi

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  1. Sonia Zorzet
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  2. Laura Perissin
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  3. Valentina Rapozzi
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  4. Sabrina Pacor
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  5. Tullio Giraldi
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Zorzet, S., Perissin, L., Rapozzi, V. et al. Effects of prolonged treatment with decarbazine on tumour metastatic potential in mice bearing Lewis lung carcinoma. Clin Exp Metast 13, 97–104 (1995). https://doi.org/10.1007/BF00133614

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  • DOI: https://doi.org/10.1007/BF00133614

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