Adriamycin-activated macrophages as tumor growth inhibitors.

Flow cytometry has been used to study the influence of Adriamycin- and Corynebacterium parvum-elicited cytostatic macrophages on the cell cycle of HeLa cells. Macrophages harvested from the peritoneal cavity of mice given i.p. injections of Adriamycin retain cytostatic activity for 3 to 4 days in vivo. Many of these macrophages fluoresced with the red emission spectra characteristic of Adriamycin. The decline in the presence of macrophages exhibiting red fluorescent cytoplasmic particles paralleled the loss in cytostatic activity. Drug-induced cytostatic macrophages exhibited at least as high a level of growth inhibition as did C. parvum-activated cells. In contrast to the apparent G1 block of HeLa cells which resulted from interaction wih C. parvum-activated macrophages. Adriamycin-stimulated macrophages inhibited growth in the G2-M phase characteristic of the free drug. Multiple freeze-thaw cycles removed all activity from C. parvum macrophages but had no influence on the Adriamycin-elicited effector cell activity. The data suggest that in vivo drug storage by macrophages may represent an important step in tumor cell destruction by Adriamycin.