Cytotoxic Activity of in Vitro Activated Cyclophosphamide on Tumors in Primary Culture

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Abstract
An in vitro method for testing the cytotoxic activity of compounds active through the formation of metabolites is described, and cyclophosphamide (CPA) has been chosen as a « model » substance. A tumor primary explant, cultured in a Rose chamber, was treated for 90 min at 37 °C with CPA in the presence of microsomal enzymes (105,000 × g liver fraction) and their cofactors. At the end of the incubation, the medium was removed and changed. Appropriate controls are concurrently carried out through the procedure. The cytotoxic effect of CPA is evaluated 24 h after the treatment. Primary explants from both mammary tumors of (C3H × O20)F1 mice and human ovary tumors were sensitive to CPA under our experimental conditions. The significance of this procedure for in vitro characterization of tumor sensitivity to antineoplastic agents which requires hepatic biotransformation is emphasized.