Oxygen radicals and asbestos carcinogenesis.

Moyer, Valerie D.; Cistulli, Cheryl A.; Vaslet, Charles A.; Kane, Agnes B.

doi:10.1289/ehp.94102s10131

Cited by 23 publications

(7 citation statements)

References 37 publications

(34 reference statements)

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“…More recently, it has been suggested that the degree of aneuploidy in cells reflects well the cell's proclivity for genomic instability [Duesberg et al, 1998]. In support of a role for aneuploidy in cancer causation, certain non-mutagenic carcinogens, such as asbestos, appear to transform cells by creating chromosomal mis-segregation and aneuploidy without causing DNA structural aberrations [Moyer et al, 1994]. Thus while DNA mutations may explain some cancers, it has been raised that in other malignancies an imbalance in the dosage of thousands of normal genes caused by chromosomal gains or losses may be a separately independent contributor to carcinogenesis.…”

Section: Aneuploidy and Human Cancersmentioning

confidence: 99%

Aneuploidy and cancer

Chi

Jeang

2007

J of Cellular Biochemistry

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The cell's euploid status is influenced by, amongst other mechanisms, an intact spindle assembly checkpoint (SAC), an accurate centrosome cycle, and proper cytokinesis. Studies in mammalian cells suggest that dysregulated SAC function, centrosome cycle, and cytokinesis can all contribute significantly to aneuploidy. Of interest, human cancers are frequently aneuploid and show altered expression in SAC genes. The SAC is a multi-protein complex that monitors against mis-segregation of sister chromatids. Several recent experimental mouse models have suggested a link between weakened SAC and in vivo tumorigenesis. Here, we review in brief some mechanisms which contribute to cellular aneuploidy and offer a perspective on the relationship between aneuploidy and human cancers.

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Section: Aneuploidy and Human Cancersmentioning

confidence: 99%

Aneuploidy and cancer

Chi

Jeang

2007

J of Cellular Biochemistry

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“…It is hypothesized that macrophages exposed to asbestos then undergo frustrated phagocytosis of elongated fibers [ 9 ]. This process generates harmful intracellular ROS leading to DNA damage, genomic instability, and ultimately malignant transformation of mesothelial cells [ 10 , 11 , 12 , 13 , 14 ]. A well-tolerated and safe agent with antioxidant properties could thus potentially be used to prevent the development of malignant mesothelioma (MM) in asbestos-exposed populations in a chemopreventive context.…”

Section: Introductionmentioning

confidence: 99%

Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

Pietrofesa

Velalopoulou

Albelda

et al. 2016

IJMS

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Abstract:The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs) were exposed to crocidolite asbestos fibers (20 µg/cm 2 ) and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA), and levels of 8-iso Prostaglandin F2α (8-isoP). We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM) 4-h prior to asbestos exposure. We observed a significant (p < 0.0001), time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time.LGM2605 treatment significantly (p < 0.0001) reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%-88% and 41%-73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment.LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.

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“…Recent in vitro and in vivo studies demonstrated that the mutagenic and tumorigenic effects of particles and fibers in the lung are closely linked to the formation of ROS (4)(5)(6)(7)(8). ROS generate different types of DNA modifications, including single strand breaks in the DNA double helix, 8-oxoguanine (8-oxoGua), the most frequently occurring mutagenic base modification, and various other mutagenic DNA oxidation products (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure.

Nehls

Seiler

Rehn

et al. 1997

Environ Health Perspect

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Exposure of rats to quartz (or various other particles) can lead to the development of lung tumors. At the moment, the mechanisms involved in particle-induced tumor formation are not clarified. However, it is suggested that inflammation, in conjunction with the production of reactive oxygen species (ROS) and an enhancement of epithelial cell proliferation, may play a key role in the development of lung tumors. ROS induces 8-oxoguanine (8-oxoGua) and other mutagenic DNA oxidation products, which can be converted to mutations in proliferating cells. Mutation formation in cancer-related genes is a critical event with respect to tumor formation. In this study we investigated the effects of quartz (DQ1 2) and of the nontumorigenic dust corundum on the induction of 8-oxoGua in the DNA of rat lung cells, as well as on cell proliferation and pulmonary inflammation. Wistar rats were exposed by intratracheal instillation to quartz (2.5 mg/rat) or corundum (2.5 mg/rat) suspended in physiological saline; control animals exposed to physiological saline or left untreated. Measurements were carried out 7, 21, and 90 days after the exposures. 8-oxoGua levels were determined in lung tissue sections at the single cell level by immunocytological assay using a rabbit anti-8-oxoGua antibody. After exposure to quartz, 8-oxoGua levels were significantly increased at all time points of investigation. Additionally, we observed inflammation and an enhanced cell proliferation. Exposure to corundum had no adverse effects on the lung; neither increased 8-oxoGua levels nor enhanced cell proliferation or inflammation were detected. These observations support the suggestion that inflammation associated with increased 8-oxoGua levels in lung cells and increased cell proliferation is an important determinant for particle-induced development of lung tumors in the rat.

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Oxygen radicals and asbestos carcinogenesis.

Cited by 23 publications

References 37 publications

Aneuploidy and cancer

Aneuploidy and cancer

Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure.

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