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Differences in Drug Sensitivity among Tumor Cells from Parental Tumors, Selected Variants, and Spontaneous Metastases¹

Cancer Metastasis and Treatment Laboratory, National Cancer Institute Frederick Cancer Research Center, Frederick, Maryland 21701

Eradication of drug-resistant tumor foci is essential to the successful treatment of metastasis with chemotherapeutic agents. In this study, we examined the in vitro sensitivity to a variety of chemotherapeutic agents of tumor cells from parental tumors, from their in vitro-cloned populations, and from their spontaneous metastases. Three murine tumors were studied: the B16 melanoma; the K-1735 melanoma; and the UV-2237 fibrosarcoma. In addition, we also examined the in vitro drug sensitivity of cells from the A-375 human melanoma and its various subpopulations. The drugs used in these studies were Adriamycin, 4'-(9-acridinylamino)methanesulfon-m-anisidine, bleomycin, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, vincristine, and vindesine. The growth-inhibiting activity of the drugs was recorded in values which were derived from plotting the logarithm of the drug concentration versus the growth rate (percentage of control) of the treated cells and which determined the molar concentration of drugs necessary to reduce doubling by 50%.

Our results demonstrate that differences in drug response exist among cells populating a parental tumor (in vitro cloned), between the parental line and its metastatic subpopulations (in vivo-selected lines), and among the various spontaneous metastases. These extensive differences in drug sensitivity could have profound implications for the treatment of metastases with cytotoxic drugs.

¹ This work was sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-75380 with Litton Bionetics, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

² Recipient of a Yamagiwa-Yoshida Memorial International Cancer Study Grant awarded by the International Union Against Cancer during which tenure this work was undertaken. Present address: Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Toshima-ku, Tokyo 170, Japan.

³ To whom requests for reprints should be addressed.

Received 3/ 9/81. Accepted 4/23/81.

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