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Chemotherapie eines Hodentumors in der Nacktmaus

  • O. K. Schlappack
  • J. I. Delic
  • C. Bush
  • G. G. Steel
Conference paper

Zusammenfassung

Die menschliche Hodentumorlinie GCT 27, als subkutane Tumoren in männlichen Nacktmäusen wachsend, wurde zur Untersuchung einer Reihe von chemotherapeutischen Substanzen verwendet. Die Tumoren wurden in mit 5 Gy ganzkörperbestrahlten Tieren passagiert, wobei die mediane Angehrate 62% (39–73%) und die mediane Tumorverdopplungszeit 14 Tage (7–28 Tage) betrug. Für Bleomycin, Cisplatin und Carboplatin wurden steile Dosiswirkungskurven gefunden. Während Bleomycin erhebliche Gewichtsverluste verursachte, wurden mit Cisplatin maximale Wachstumsverzögerungen mit völlig untoxischen Dosen erzielt. Die Dosis von Carboplatin, die eine maximale Wachstumsverzögerung bewirkte, verursachte bereits eine 25prozentige Letalität. Vinblastin und Etoposid erwiesen sich in tolerabler Dosierung als unwirksam. Auch die fraktionierte Gabe von Etoposid, oder die Kombination mit dem Kalziumantagonisten Verapamil, führte nicht zu günstigeren Resultaten, jedoch die Kombination von 20 mg/kg Etoposid mit 2 mg/kg Cisplatin, beides, für sich allein gegeben, unwirksame Dosen, führte zu einer Wachstumsverzögerung, die jener nach Applikation höherer Cisplatindosen vergleichbar war. Dieser letzte Befund läßt sich vielleicht damit erklären, daß Etoposid als Hemmer der DNA-Topoisomerase II mit der Reparatur, der durch Cisplatin verursachten DNA-Brückenbildungen, interferiert.

Abstract

The human germ cell tumor cell line GCT 27, growing as subcutaneous xenograft tumors in male nude mice, was used in the 4th and 5th passage to study responses to chemotherapeutic drugs. Recipient mice received 5 Gy whole-body irradiation immediately before tumor transplantation. The median take rate was 62% (range 39%–73%) and the median volume doubling time was 14 days (range 7–28 days). For bleomycin, cisplatin, and carboplatin the growth delay was clearly dose dependent. Bleomycin caused substantial weight loss at doses above 75 mg/kg, whereas a good response to cisplatin was obtained without toxic effects. Vinblastine and etoposide exerted no effect when given in nontoxic doses. The response to etoposide was not improved either by fractionated treatment or by combination with verapamil. However, the combination of 20 mg/kg etoposide and 2 mg/kg cisplatin, which when given alone were ineffective, led to a growth delay that was equal to that observed following administration of higher cisplatin doses. This effect may be explained by the fact that etoposide, as an inhibitor of DNA topoisomerase II, may interfere with the repair of DNA interstrand crosslinks caused by cisplatin.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • O. K. Schlappack
  • J. I. Delic
  • C. Bush
  • G. G. Steel

There are no affiliations available

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