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The Effect of Cyclophosphamide and Other Drugs on the Incidence of Pulmonary Metastases in Mice¹

Division of Radiobiology Research, Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

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 an 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, however, greatly increased lung colony formation (by a factor of approximately 100). This enhancement in lung colony formation was maximal when the drug was given 24 hr prior to the injection of tumor cells, but was seen as early as 2 hr and persisted as long as 8 weeks prior to the tumor cell injection.

The degree of enhancement of lung colony formation was related to the dose of cyclophosphamide and was present in weanling as well as adult mice. This enhancement was not significantly reversed by anticoagulation with either 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, however, does not appear to be mediated either by specific immunological or clotting factors.

¹ This investigation was supported by USPHS Research Grants CA-15201 and CA-10372 from the National Cancer Institute.

² Present address: Division of Radiation Therapy, Department of Radiobiology, Stanford University School of Medicine, Stanford, Calif. 94305.

³ To whom requests for reprints should be addressed.

Received 7/23/76. Accepted 10/ 8/76.

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