Oxygen Radicals and Asbestos Carcinogenesis

Abstract

Asbestos fibers have been shown to generate reactive oxygen species using a variety of in vitro assays. It is hypothesized that these highly reactive metabolites mediate the development of malignant mesothelioma induced by asbestos fibers. DNA is a potential target of oxidant attack. Adaptive responses to oxidant injury have been described during exposure of mesothelial cells to asbestos fibers in vitro. Failure of these adaptive responses may lead to genetic instability and alterations in oncogenes and tumor suppressor genes that confer a proliferative advantage to emerging neoplastic mesothelial cells.

Origins of Injection-Site Sarcomas in Cats: The Possible Role of Chronic Inflammation—A Review

“…There was evidence of oxidative and nitrative stress in these animals as a result of implantation. Oxidative stress is associated with the process of carcinogenesis [365–370]. …”

Aneuploidy and cancer

“…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.…”

The Cytotoxicity of Microglass Fibers on Alveolar Macrophages of Fischer 344 Rats Evaluated by Cell Magnetometry, Cytochemisry and Morphology

“…It is also suggested that the chemical composition of fibers contributes to their toxicity as much as the physical properties (31). Moyer et al (32) suggested that the iron included in asbestos generates active oxygen through the Harber-Weiss reaction, which causes DNA injury and carcinogenesis. Although active oxygen species may also be generated in other minerals, the lesser iron content generates lesser amounts of active oxygen species, resulting in lower toxicity.…”