Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies.

Abstract:

:Although the association between exposure to asbestos fibers and the development of lung cancer and mesothelioma has been well established in humans, the carcinogenic potential of other natural and man-made fibers/particles is not clear. Various in vitro genotoxicity studies have been employed to assess their in vivo carcinogenic potential. Studies using mammalian cell models have suggested that fiber dimensions, surface properties, physical durability, and cell and tissue responses are important criteria for the carcinogenicity of the fibers. Studies using oncogenic transformation as an endpoint have shown that asbestos fibers can induce malignantly transformed foci in certain rodent cells and that oxygen radicals are important in the toxic, oncogenic transforming, and mutagenic effects of asbestos fibers. The mutagenicity of asbestos in mammalian cells have been demonstrated using several model systems that can detect large multilocus deletions. These findings provide a direct link between chromosomal abnormalities that have frequently been demonstrated in fiber-exposed human and rodent cell lines and carcinogenicity in vivo. Although asbestos has not been shown to malignantly transform primary human epithelial cells, it can induce neoplastic conversion of immortalized human bronchial epithelial cells in a stepwise fashion and provides a unique opportunity to assess the molecular alterations associated with each stage of the neoplastic process.

journal_name

Inhal Toxicol

journal_title

Inhalation toxicology

authors

Hei TK,Xu A,Louie D,Zhao YL

doi

10.1080/08958378.2000.11463207

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

141-7

eissn

0895-8378

issn

1091-7691

journal_volume

12 Suppl 3

pub_type

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