Inability of aflatoxin B1 to stimulate arachidonic acid metabolism in human polymorphonuclear and mononuclear leukocytes.
Previous reports have suggested that aflatoxin B1 (AFB1) is a membrane-active compound capable of mediating chromosomal damage through release of toxic oxygen radicals and arachidonic acid metabolites by human leukocytes. Thus, the ability of AFB1 to stimulate directly arachidonic acid metabolism and generate a respiratory burst in human neutrophils and monocytes was examined. AFB1 (10(-8)-10(-6) M) failed to induce [3H]arachidonate release from prelabeled human neutrophils or mononuclear leukocytes. Similarly AFB1 exposure at these concentrations failed to stimulate the production of either thromboxane (TX)B2 or leukotriene (LT)B4 from adherent monocytes. AFB1 was also ineffective in stimulating respiratory burst activity as measured by superoxide anion (O2.-) formation in both neutrophil and mononuclear leukocytes. We conclude that AFB1 is unable to stimulate either arachidonic acid metabolism or initiate a respiratory burst of human leukocytes. Therefore, it appears that these pathways are not involved in the genotoxic mechanisms of AFB1 as previously suggested.
Geissler
F T
FT
Department of Biological Structure, University of Washington, Seattle 98195.
Henderson
W R
WR
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis
D000348:Aflatoxins; D001095:Arachidonic Acids; D013481:Superoxides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D003571:Cytochalasin B; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016604:Aflatoxin B1