EFFECTS OF PROLONGED TREATMENT WITH DECARBAZINE ON TUMOR METASTATIC POTENTIAL IN MICE BEARING LEWIS LUNG-CARCINOMA

The effects of decarbazine on tumour growth and metastatic disseminati on 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 trea tment. In contrast, dacarbazine significantly inhibits the formation o f lung metastasis. The proportion of mice with metastasis decreases fo r an increasing number of transplant generations of treatment, and aft er 10 transplant generations of treatment metastatic capacity is compl etely lost in immunocompetent mice. The reduction in metastatic potent ial is relatively stable, being retained for three successive transpla nt generations without treatment. The metastatic potential of treated tumours in immunosuppressed mice is substantially similar to that in i mmunocompetent hosts, indicating that chemical xenogenization of tumou r cells does not occur as reported for transplantable mouse leukaemias . The results obtained using clonally selected tumour lines with diffe rent metastatic potential rule out the selection by dacarbazine of tum our cell sublines with reduced metastatic potential as the mechanism o f the drug's action. Upon prolonged treatment, dacarbazine appears to cause a rather stable and dramatic loss in metastatic potential, not a ccompanied by resistance, which might be attributed to genotypic alter ation(s) of tumour cells, and which might participate into the clinica l effects of the drug.