In Vitro Assessment of Cytotoxic Agents in Murine Cancers: Comparison Between Antiproliferative and Antimetabolic Assays2

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Abstract
Different methods were compared for the in vitro evaluation of the therapeutic effects of the antineoplastic agents doxorubicin, cisplatin, fluorouracil, and vinblastine sulfate in a model system of murine tumor cell lines consisting of L1210 leukemia, P815 mast cell leukemia, and B16 melanoma. Excellent correlations were found with the in vivo effects with the use of a soft agar clonogenic assay, irrespective of the method of growth assessment (i.e., visual colony counting or incorporation of tritiated thymidine in proliferating colonies). Drug effects on the proliferation of tumor cell lines in liquid medium frequently led to an overestimation or underestimation of the actual in vivo effects. Direct incorporation of the radiolabeled precursors thymidine, uridine, and leucine after pretreatment with drugs always led to the prediction of resistance and was therefore considered un-reliable.