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Tumor Cytokinetics in the Presence of Normal, Alloimmune, or Bacillus Calmette-Guérin-activated Host Cells Simultaneously Assayed in Vivo and in Vitro¹

Department of Pathology, College of Medicine, University of Florida, Gainesville, Florida 32610

Rates of tumor cell loss, replication, and growth were determined simultaneously for P-815 mastocytoma cells placed in culture or transplanted as a peritoneal ascites tumor. Cytokinetic parameters were concordant in vitro to in vivo for P-815 cells growing in the presence of syngeneic DBA/2 resident or proteose peptone-elicited macrophages and under allogeneic C57BL/6 nonimmune conditions. Under alloimmune conditions, measured parameters differed in vitro from in vivo but conclusions were consistent in that alloimmune host cells were cytolytic and cytostatic and caused tumor regression. In contrast, syngeneic Bacillus Calmette-Guérin-activated macrophages were cytolytic and cytostatic in vitro but not in vivo despite equivalent or greater effector to target ratios, presence or absence of endotoxin in the tumor inoculi, or changes in the injection schedule of Bacillus Calmette-Guérin. Similarly, Bacillus Calmette-Guérin-activated macrophages were cytolytic in vitro but not in vivo when admixed with tumor cells prior to injection into the leg. This study is the first simultaneously conducted cytokinetic analysis of a common pool of labeled tumor cells growing in vitro and in vivo using randomly selected mice as donors of host effector cells or as recipients of tumor transplantation. It demonstrates that activated macrophages which are cytolytic and cytostatic in vitro for P-815 cells may not function analogously in vivo in controlling tumor growth.

¹ This work was supported by grant IM-441 from the American Cancer Society.

² To whom requests for reprints should be addressed, at Department of Pathology, College of Medicine, P. O. Box J-275, University of Florida, Gainesville, FL 32610.

Received 4/16/86. Revised 11/ 7/86. Revised 1/20/87. Accepted 1/23/87.