Tumor promoters stimulate the formation of 1,2-diacylglycerol in murine peritoneal macrophages: a possible mechanism for stimulating superoxide anion radical production.
The formation of 1,2-diacylglycerol (DAG), a known stimulator of superoxide anion radical (O2-.) production in inflammatory cells, was assessed in murine peritoneal macrophages following treatment in vitro with tumor promoters. Addition of phorbol-12-myristate-13-acetate (PMA, 1-100 ng/ml) to resident peritoneal macrophage cultures from CD-1 female mice resulted in a 3- to 7-fold increase in [3H]DAG formation. The response was observed from 15 min to 2 h following the addition of PMA. At concentrations at which they stimulate O2-. production, PMA and other tumor promoters such as mezerein, phorbol-12,13-dibutyrate and 4-O-methyl-PMA stimulated the formation of [3H]DAG. Similar results were obtained when thioglycollate-elicited macrophages were used. Concurrent with the formation of [3H]DAG was a release of [3H]choline equivalents from the resident peritoneal macrophages treated with tumor promoters. The calcium ionophore A23187 did not stimulate O2-. production of [3H]DAG formation in resident peritoneal macrophages. These results demonstrate that tumor promoters stimulate the accumulation of DAGs in murine peritoneal macrophages at concentrations at which they stimulate O2-. production and suggest a mechanism by which tumor promoters such as mezerein, which are weak activators of protein kinase C, may indirectly stimulate O2-. production.
Czerniecki
B J
BJ
UMDNJ-Robert Wood Johnson Medical School, Department of Environmental and Community Medicine, Piscataway, NJ 08854.
Witz
G
G
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D002273:Carcinogens / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D005260:Female; D005989:Glycerides / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*
C011439:1,2-diacylglycerol; D002273:Carcinogens; D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D013481:Superoxides; D002794:Choline