EFFECT OF CYCLOPHOSPHAMIDE AND OTHER DRUGS ON INCIDENCE OF PULMONARY METASTASES IN MICE

Abstract

A study was made of the effect of various cytotoxic drugs on the ability of i.v.-injected KHT sarcoma cells to form lung colonies in syngeneic C3H mice. Some enhancement of the number of lung colonies following i.v. injection was seen following pretreatment of the mice with actinomycin D and mithramycin, while pretreatment with vinblastine, bleomycin, methotrexate, cytosine arabinoside or 5-fluorouracil had little or no effect on lung colony formation. Pretreatment of the mice with cyclophosphamide increased lung colony formation (by a factor of .apprx. 100). This enhancement in lung colony formation was maximal when the drug was given 24 h prior to injection of tumor cells, but was seen as early as 2 h and persisted as long as 8 wk prior to tumor cell injection. The degree of enhancement of lung colony formation was related to the dose of cyclophosphamide and was present in weanling and adult mice. This enhancement was not significantly reversed by anticoagulation with aspirin or warfarin. Immunosuppression by whole body irradiation did not affect the number of lung colonies seen in cyclophosphamide-treated mice. The mechanism by which cyclophosphamide enhances metastatic tumor growth within the lung is not known. The major effect does not appear to be mediated either by specific immunological or clotting factors.