The heterogeneity with respect to the sensitivity to a cytotoxic agent of clones derived from a mouse fibrosarcoma tumor (MCA-F?) and its individual metastatic lung colonies has been examined. After 1 hr exposure of mitomycin C (MMC), the plating efficiency (PE) of parental tumor cell clones and metastatic cell clones were measured respectively, suggesting that the degree of clonal heterogeneity of primary tumor cells which showed different ancholage-independency was lower than that of metastatic tumors. The drug sensitivity of parental tumor cell clones also showed their heterogeneity and in the individual metastatic lung tumor cell clones as well, but with a rather high resistance. One (MCA-F-M2) out of 4 colonies in the lung, especially showed significantly high % PE in a clonogenic assay using 1 hr MMC exposure at 0.1 μg/ml concentration (mean % PE=19.7; P<0.005) and its clones showed almost the same homogeneous sensitivity within a growing colony in the lung. While, there existed not a small population of drug sensitive clones within these metastatic lesions. These findings indicate the clonal chemotherapeutic heterogeneity in metastatic lesions, and may provide, serious implications for the administration of antitumor drugs on the early differentiation of tumors
