Different sensitivity to cytostatic drugs of primary tumor and metastasis of the Lewis carcinoma.

Differences in cytostatic sensitivity between subcutaneously transplanted Lewis lung carcinomas and metastases from them were studied in vitro. Sensitivity to vinblastine sulphate and melphalan was determined as the reduction of the incorporation of H3-thymidine into drug-treated cells compared with control cells. The main result of the present study is that tumor cells obtained from pulmonary metastases are more sensitive to cytostatic drugs in vitro than are the cells obtained from the corresponding subtaneous tumors. When cells from pulmonary metastases are transplanted subcutaneously, the sensitivity of the resulting tumor closely resembles that of other subcutaneous tumors. However, when the tumor cells have been passed through many cycles where the pulmonary metastases from subcutaneous tumors were re-transplanted subcutaneously and then allowed to metastasize again, a selection of tumor cells has apparently occurred: they have become more sensitive even when grown subcutaneously. Different explanations of this phenomenon are discussed.