Possible cellular and molecular mechanisms for asbestos carcinogenicity

Abstract

Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free radicals from the fiber surface; indirect effects, following the interaction of fibers with inflammatory cells can result in the production of cellular mediators such as cytokines and various reactive oxygen species. As a result, target cells may be induced to proliferate and/or sustain genetic alterations, which lead to tumor development.

Oxygen radicals and asbestos carcinogenesis.

“…Asbestos and other mineral fibers are negative in these assays. When examined for their ability to produce point mutations at specific loci in mammalian cells, mineral fibers were also found to be negative or marginally positive (27). Chromosomal alterations, including breaks and translocations, may be produced by oxidants; these changes can be detected by cytogenetic analysis of cells arrested in metaphase.…”

Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence.

“…Both normal and transformed mesothelial cells express and respond to a variety of growth factors and growth factor receptors (5), which can act as oncogenes if overexpressed or inappropriately expressed. However, a specific oncogene involved in mesotheliomas has not yet been identified (5).…”

“…To date, the role of EGF-R expression in the development of mesothelioma has not been thoroughly investigated. In addition, platelet-derived growth factor-alpha (PDGF-ox) also is located on human chromosome 7 (21), and a role for this growth factor in the development of mesothelioma has been suggested (5).…”

“…Although asbestos and other mineral fibers do not induce gene mutations, they are active as chromosomal mutagens (5,23,24). Chromosomal gains and losses and chromosomal deletions are induced increase in the number of cells with abnormalities including lagging chromosomes, bridges, and sticky chromosomes.…”

“…Asbestos can heritably transform cells in culture leading to neoplastic transformation (5,28). Furthermore, asbestos-induced cell transformation is dependent on fiber size as is asbestos carcinogenicity, in vivo (28).…”