Tumor Chemotherapy: Efficacy Dependent on Mode of Growth2

Abstract
Cell survival curves for P815X2 mastocytoma cells after 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) have been obtained at various growth stages (log, plateau, and degenerating) and modes of tumor growth (culture, ascites, and solid). In culture and ascites forms, log-phase cells exhibited a well-defined shoulder region on the survival curves, whereas plateau and degenerating phases had a markedly reduced shoulder. In solid form, the cells showed only a small shoulder region. The smallest tumors, of the solid form, were the most sensitive to BCNU; however, resistance did not continuously progress as tumor size increased. Sensitivity to the drug did not appear to be causally related to cell density. The clonogenic potential as measured in vitro, remained >90% for all stages and modes of tumor cell growth. In contrast, the tritiated thymidine labeling indices varied markedly. Clonogenic potential appeared unrelated to the initial proliferative state of the tumor cells. The differences in P815X2 cell survival between solid tumors and either culture or ascites forms overshadowed variations due to stage of cell growth or those between solid tumors of various sizes. These observations along with the results of the tritiated thymidine labeling studies, suggested that the relative resistance of P815X2 mastocytoma cells in solid form to BCNU is, at least in part, due to failure of the drug to reach substantial numbers of target cells in the tumor.