author={Roel P.F. Schins},
  journal={Inhalation Toxicology},
  pages={57 - 78}
  • R. Schins
  • Published 1 January 2002
  • Biology
  • Inhalation Toxicology
With regard to genotoxicity testing and cancer risk assessment, particles and fibers form a rather specific group among all toxicants. First, the physicochemical behavior of fibrous and nonfibrous particles is usually very different from that of nonparticulate, chemical carcinogens. Reactive oxygen species (ROS) are believed to play a major role in primary genotoxicity of particles, which may derive from their surface properties, the presence of transition metals, intracellular iron… 

Genotoxicity of Poorly Soluble Particles

Poorly soluble particles such as TiO2, carbon black, and diesel exhaust particles have been evaluated for their genotoxity using both in vitro and in vivo assays, since inhalation of these compounds

Inhaled particles and lung cancer. Part A: Mechanisms

Since most of the proposed molecular mechanisms underlying particle‐related carcinogenesis have been derived from in vitro studies, there is a need for future studies that evaluate the implication of these mechanisms for in vivo lung cancer development and transgenic and gene knockout animal models may provide a useful tool.

Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity

Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP- induced injury can be developed.

Solid-Phase Environmental Genotoxicity: In Vivo Veritas!

Specific genotoxicity of solid particles are discussed by using three different examples, including Medicinal muds used in balneotherapy and medical wellness consisting of suspensionscause dermal exposure of patients, and carbon nanotubes do not show any genotoxic effects, but lack of their carcinogenicity is still debated.

Cellular responses to nanoparticles: Target structures and mechanisms

An integrated research protocol is proposed to identify fundamental cellular responses to NP in order to complement current toxicological screening strategies with a mechanism-based approach.

Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity.

The observed spectrum of genotoxic effects shows similarities with those reported for asbestos fibres, and frustrated phagocytosis, which is involved in asbestos-induced pathology, has been observed for specific CNTs as well.

Pathways for Nanoparticle (NP)-Induced Oxidative Stress

Through physicochemical characterization and understanding of the multiple signaling cascades activated byNP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed.



Mechanisms of fiber-induced genotoxicity.

  • M. Jaurand
  • Biology
    Environmental health perspectives
  • 1997
Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption.

8-Hydroxyguanosine formed in human lung tissues and the association with diesel exhaust particles.

Particles, inflammation and respiratory tract carcinogenesis.

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

Investigation of the effects of quartz 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 support the suggestion that inflammation associated with increased 8-OxoG Hua levels in lung cells and increased cell proliferation is an important determinant for particle-induced development of lung tumors in the rat.

Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies

It is shown that asbestos 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 neoplastics process.

Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and apoptosis in mesothelial cells.

It is concluded that phagocytosis is important and perhaps necessary for asbestos-induced injury to mesothelial cells, and asbestos increased intracellular oxidation, DNA strand breakage, and apoptosis.

Mechanisms and mediators in coal dust induced toxicity: a review.

DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe3+].

Results indicate that genotoxic effects of these fibers may correspond to their capacity to complex iron at the surface, as measured as thiobarbituric acid-reactive products of deoxyribose and more covalently closed, circular DNA strand scission.

Occupational and Environmental Factors Enhancing the Genotoxicity of Asbestos

The study suggests that smokers occupationally exposed to asbestos and domestically to kerosene soot are at higher risk for the early development of asbestos-induced diseases.

The role of free radicals in asbestos-induced diseases.