Quartz hemolysis as related to its surface functionalities

MarylandThe carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type 11 cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type 11 hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type 11 cells. Immunohistochemical localization of TGF-,B1 precursor in alveolar type 11 cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides. -Environ Health Perspect 102(Suppl 10): 159-164(1994)

Section: Introductionmentioning

confidence: 90%

Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.

Saffiotti

Daniel

Mao

et al. 1994

“…Polyvinylpyridine-N-oxide is thought to detoxify silica by acting as a proton acceptor and shielding the SiOH groups on quartz. Nolan et al (88) have proposed that the negative surface charge of the SiO-groups is critical to cytotoxicity. It is possible that this negative charge allows silica to interact with scavenger receptors on alveolar macrophages (80,89).…”

Section: Mechanisms Of Silica and Coal Pathogenicitymentioning

confidence: 99%

Silicosis and coal workers' pneumoconiosis.

Castranova

Vallyathan

2000

309

176

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; o) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms.

“…The first is that silanol groups (SiOH) can form hydrogen bonds with the oxygen or nitrogen groups in biologic membranes causing loss of membrane integrity and cell death (6). A second theory is that the negative surface charge associated with SiO-groups is critical to cytotoxicity (7). A third theory is that radical sites are present on the surface of silica that may contribute to its ability to injure lung tissue (8).…”

Section: Introductionmentioning

confidence: 99%

Generation of oxygen radicals and mechanisms of injury prevention.

Castranova

1994

Exposure to crystalline silica can result in damage to the lung parenchyma and scarring that can lead to fibrosis. Pulmonary damage may be the direct consequence of toxic interaction between quartz particles and cell membranes, or it may be due to silica-induced production of oxidant species by pulmonary phagocytes, that in turn overwhelms pulmonary antioxidant systems and causes lung injury. Data indicate that grinding or fracturing quartz particles breaks Si-O bonds and generates Si and Si-0 radicals on the surface of the cleavage planes. Upon contact with water, these silica-based radicals can generate hydroxyl radicals (OH). These surface radicals decay as fractured silica dust is aged. Freshly fractured quartz is significantly more potent than aged silica in directly causing lipid peroxidation, membrane damage, and cell death. Furthermore, freshly ground silica is a more potent stimulant of alveolar macrophages than aged silica. This silica-induced activation results in the production of superoxide (O°), hydrogen peroxide (H202), nitric oxide (NO), and other oxidant species that can damage lung cells. Tetrandrine, an herbal medicine that exhibits antifibrotic activity in rat models of silicosis, effectively blocks the ability of quartz to stimulate oxidant release from pulmonary phagocytes.-Environ Health Perspect 102(Suppl 10): 65-68 (1994)