Enhanced activity of peritoneal cells after aclacinomycin injection: effect of pretreatment with superoxide dismutase on aclacinomycin-induced cytological alterations and antitumoral activity.
Peritoneal macrophages from mice injected with aclacinomycin (ACM) (4 mg/kg, i.p.) showed increased functional activity, as assessed by increased antitumoral activity in vitro and in vivo and zymosan-triggered chemoluminescence. They also showed ultrastructural signs of activation (increased number of cytoplasmic organelles), and atypical alterations (giant vacuoles and giant lysosomes containing heterogenous myelinoid bodies, lipofuscine-like substance, cytoplasmic debris, and a fine granular material). As these atypical alterations could be due to the generation of superoxide following ACM injection, superoxide dismutase (SOD) was injected 1 h prior to ACM administration. Neither the morphological characteristics of activation, nor the enhanced metabolic and antitumoral activities induced by ACM were affected by SOD pretreatment, but the atypical alterations were inhibited in a dose-dependent manner. Heat-inactivated SOD did not prevent their appearance. The atypical alterations were not found in peritoneal macrophages from talc or lipopolysaccharide-injected mice, but they were present in Adriamycin-treated mice and were also prevented by SOD pretreatment, indicating that the alterations are due to anthracycline treatment. Finally, [125I]SOD was phagocytized by peritoneal macrophages in vitro and in vivo and not by L1210 tumoral cells, explaining why the atypical alterations induced by ACM were no longer seen after SOD pretreatment. The unchanged direct oncostatic activity of ACM following SOD pretreatment suggests that this combination may have some wider perhaps clinical, potential.
Bravo-Cuellar
A
A
Institut du Cancer et d'Immunogénétique (CNRS UA 04-1163, Université de Paris-Sud, Hôpital Paul-Brousse, Villejuif, France.
Balercia
G
G
Levesque
J P
JP
Liu
X H
XH
Osculati
F
F
Orbach-Arbouys
S
S
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D013627:Talc / Q000494:pharmacology
D008070:Lipopolysaccharides; C011157:aclacinomycins; D013627:Talc; D015250:Aclarubicin; D013482:Superoxide Dismutase