Correlation of tumor growth inhibitory activity of macrophages exposed to adriamycin and adriamycin sensitivity of the target tumor cells.

Abstract

Variant cell lines of the murine fibrosarcoma UV-2237, selected for doxorubicin [adriamycin (ADM)] resistance, were used to study the tumoricidal activity of macrophages that had been exposed to ADM. Free ADM (0.01-1 microgram/ml) was cytotoxic to the sensitive UV-2237M parent and to the partially sensitive UV-2237M-revertant cell lines, whereas the ADM-resistant UV-2237M ADMR line was unaffected by these levels of ADM. Macrophages harvested from the peritoneal cavities of mice given ip injections of 10 mg ADM/kg body weight 1 day or 4 days previously inhibited proliferation of the 3 cell lines, an effect that was directly correlated to the degree of ADM sensitivity of each cell line. Macrophages exposed in vitro to ADM (from 0.01 to 1 microgram/ml) inhibited the growth of, and eventually were cytolytic to, the parent and the revertant cell lines; these ADM-exposed macrophages did not affect the UV-2237M-ADMR cell line. The correlation between the antitumor effects of macrophages exposed to ADM and the ADM susceptibility of tumor cells suggests that ADM-exposed macrophages exert their effect by the release or transfer of the stored drug.

• Authors: R Giavazzi, C D Bucana, I R Hart
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 73 Issue 2 Pg. 447-55 (Aug 1984) ISSN: 0027-8874 [Print] United States
• PMID: 6589436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Doxorubicin

Topics

• Animals
• Cell Division (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (pharmacology)
• Fibrosarcoma (immunology, physiopathology)
• Macrophages (drug effects, immunology)
• Mice
• Mice, Inbred Strains
• Sarcoma, Experimental (immunology, physiopathology)