Crocidolite-Induced Reactive Oxygen Metabolites Generation from Human Polymorphonuclear Leukocytes

Abstract

In order to study the mechanism of carcinogenicity of crocidolite asbestos, we have investigated the species of reactive oxygen metabolites (ROM) induced by crocidolite from human polymorphonuclear leukocytes (PMN) utilizing both an electron spin resonance (ESR) spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and a luminol-dependent chemiluminescence (CL) method. The present study confirms the generation of OH . from human peripheral blood PMN stimulated by UICC crocidolite utilizing ESR. In addition, PMN incubated with 25-400 μg/ml of crocidolite produced CL, the intensity of CL increasing in a dose-dependent manner. Superoxide dismutase, catalase, and dimethyl sulfoxide, which are scavengers of O 2 −, H 2O 2, and OH . , respectively, inhibited the production of crocidolite-stimulated CL from PMN, also in a dose-dependent manner. Sodium azide, an inhibitor of myeloperoxidase (MPO) to produce OCl −, also inhibited CL production. These results suggest the involvement of O 2 −, H 2O 2, OH . , and OCl − in the production of CL by crocidolite-stimulated PMN. In conclusion, it is proposed that OH . is a key ROM species in the mechanism of crocidolite-induced carcinogenesis.