Detection of induced tumour-resistance to cyclophosphamide by the in vitro short term test

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Abstract
Treatment of the solid Walker carcinosarcoma of the rat for a period of one year with cyclophosphamide (40 mg/kg at each passage; tumours were transplanted weekly) resulted in the formation of a cyclophosphamide-resistant tumour cell line. Without further treatment, animals injected with non-treated or cyclophosphamide pre-treated cells survived for 10 days on an average. After therapy with cyclophosphamide (2×38 mg/kg), rats with non-treated tumour cells survived 22 days whereas those with pre-treated tumours survived only for 17 days. Tumour cells which were shown to be sensitive in vivo also exhibited a larger reduction in3H-thymidine and3H-uridine incorporation in the in vitro short term test after incubation with urine from cyclophosphamide-treated rats or with 4-hydroperoxy-cyclophosphamide. The resistance to cyclophosphamide which was detected in animal experiments with Walker carcinosarcoma can therefore also be observed using the in vitro short term test. Durch Behandlung mit Cyclophosphamid wurde beim soliden Walker-Carcinosarkom der Ratte eine resistente Tumorzellinie erzeugt. Diese Resistenz zeigt sich außer im Tierexperiment auch im In vitro-Kurzzeittest nach Inkubation der Tumorzellen mit Urin Cyclophosphamid-behandelter Ratten bzw. nach Inkubation der Zellen mit 4-Hydroperoxycyclophosphamid. Somit erbringt die Testung von Tumoren im Kurzzeittest nicht nur Hinweise auf die proliferativen Eigenheiten der Tumoren, von der die Cytostaticawirkungen abhängen, sondern es lassen sich auch induzierte Resistenzen nachweisen.