← Back to Search
MECHANISMS OF GENOTOXICITY OF PARTICLES AND FIBERS
Published 2002 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
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 mobilization, and lipid peroxidation. Other aspects relevant to primary genotoxicity are particle size, shape, crystallinity (e.g., silica), and solubility, and may also include particle uptake, interaction with cell division machinery (e.g., asbestos), and the presence of mutagens carried with the particle (e.g., diesel exhaust particles, DEP). Excessive and persistent formation of ROS from inflammatory cells is considered as the hallmark of the secondary genotoxicity of nonfibrous and fibrous particles. Since lung inflammation is known to occur and persist only at sufficient particle dose, this secondary pathway is considered to contain a threshold (Greim et al., 2001). Identification of (mechanisms of) particle genotoxicity has been/can be achieved via (1) acellular assays, (2) in vitro tests, (3) in vivo studies, usually in mice or rats, and finally (4) biomarker studies in humans with (occupational) exposure. The significance of acellular assays and biomarker studies for risk assessment is limited, but has provided some mechanistic insights (e.g., in oxidant generating properties of quartz and asbestos) and may also contribute to hazard identification. In vitro studies have lead to identification of primary genotoxic properties of particles, whereas recent in vivo studies provide further support for the correlation between particle-induced lung inflammation and secondary genotoxicity. Proper risk assessment of particles necessitates identification of the relative impact of primary versus secondary genotoxicity in realistic exposure conditions. However, since it is impossible to discern between primary and secondary genotoxicity with current in vivo tests, concomitant in vitro assays are required to determine primary genotoxicity. In vivo tests should ideally be designed using different doses to allow dose-effect analysis for both inflammation and genotoxicity.
This paper references
Induction of sister chromatid exchanges (SCE) in human tracheal epithelial cells by the fractions PM-10 and PM-2.5 of airborne particulates.
C. Hornberg (1998)
Contrasting bronchoalveolar leukocyte responses in rats inhaling coal mine dust, quartz, or titanium dioxide: effects of coal rank, airborne mass concentration, and cessation of exposure.
K. Donaldson (1990)
The comet assay (single-cell gel test). A sensitive genotoxicity test for the detection of DNA damage and repair.
G. Speit (1999)
Biological markers and occupational lung disease: mineral dust-induced respiratory disorders.
P. Borm (1994)
The distinction between genotoxic and epigenetic carcinogens and implication for cancer risk.
J. Weisburger (2000)
Current cytogenetic methods for detecting exposure and effects of mutagens and carcinogens.
A. T. Natarajan (1996)
Chromosome aberrations, micronuclei, sister chromatid exchanges and cancer risk assessment
J. D. Tucker (1996)
Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals.
G. Williams (1989)
DNA single strand breaks induced by asbestos fibers in human pleural mesothelial cells in vitro
T. Ollikainen (1999)
Silica-induced micronuclei and chromosomal aberrations in Chinese hamster lung (V79) and human lung (Hel 299) cells.
R. Nagalakshmi (1995)
Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats
K. Unfried (2000)
Nuclear factor kappa-B activation by particles and fibres
R.P.F. Schins (2000)
Sequence of Events in Lung Carcinogenesis
C. H. Kennedy (1997)
Detection of mineral-dust-induced DNA damage in two mammalian cell lines using the alkaline single cell gel/comet assay.
B. Zhong (1997)
Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues
Y. Kuchino (1987)
Asbestos and cigarette smoke cause increased DNA strand breaks and necrosis in bronchiolar epithelial cells in vivo.
M. Jung (2000)
Passage of intratracheally instilled ultrafine particles into the systemic circulation of the hamster
B. Nemery (2001)
Critical role of GSH in silica-induced oxidative stress, cytotoxicity, and genotoxicity in alveolar macrophages.
Z. Zhang (1999)
Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.
N. Fatma (1991)
Pulmonary effects of inhaled ultrafine particles
G. Oberdörster (2001)
Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.
K. Szyba (1983)
Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres.
P. Howden (1996)
Diesel exhaust is a pulmonary carcinogen in rats exposed chronically by inhalation.
J. Mauderly (1987)
Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair.
H. Kasai (1986)
Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure.
P. Nehls (1997)
Oxyradicals and DNA damage.
L. Marnett (2000)
Characterization of automotive emissions by bacterial mutagenesis bioassay: a review.
L. Claxton (1983)
Iron ion-dependent modification of bases in DNA by the superoxide radical-generating system hypoxanthine/xanthine oxidase.
O. Aruoma (1989)
Micronucleus formation in V79 cells treated with respirable silica dispersed in medium and in simulated pulmonary surfactant.
X. Liu (1996)
Cytogenetic damage and occupational exposure. I. Exposure to stone dust.
R. Sobti (1991)
DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro.
L. Daniel (1995)
Iron mobilization from crocidolite asbestos greatly enhances crocidolite-dependent formation of DNA single-strand breaks in phi X174 RFI DNA.
L. Lund (1992)
Adverse health effects of PM10 particles: involvement of iron in generation of hydroxyl radical.
P. Gilmour (1996)
Role of phagocytosis in Syrian hamster cell transformation and cytogenetic effects induced by asbestos and short and long glass fibers.
T. Hesterberg (1986)
Toxicity of fibers and particles. Report of the workshop held in Munich, Germany, 26-27 October 2000.
H. Greim (2001)
Increase in mutation frequency in lung of Big Blue rat by exposure to diesel exhaust.
H. Sato (2000)
Non-animal Tests for Evaluating the Toxicity of Solid Xenobiotics
B. Fubini (1998)
Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos.
T. Quinlan (1995)
Characterizing mutagenesis in the hprt gene of rat alveolar epithelial cells.
K. Driscoll (1995)
Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly exposed to asbestos and their clinical data, occupational and non-occupational confounding factors, and cancer.
B. Marczynski (2000)
Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals.
J. Mccann (1975)
Pulmonary carcinogenicity of inhaled particles and the maximum tolerated dose.
G. Oberdörster (1997)
Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology.
K. Driscoll (1990)
Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts.
P. Howden (1996)
DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe3+].
A. Ghio (1994)
Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special reference to the presence of iron inside and outside of asbestos fiber.
S. Adachi (1994)
DNA breakage in asbestos-treated normal and transformed (TSV40) rat pleural mesothelial cells.
V. Levresse (2000)
Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells.
C. Chao (1996)
Mechanisms and mediators in coal dust induced toxicity: a review.
R. Schins (1999)
Surface chemistry and quartz hazard.
B. Fubini (1998)
Chromosomal abnormalities in soft coal open-cast mining workers.
R. Sram (1985)
Chemical mutagens: principles and methods for their detection. Vol. 8
F. Serres (1983)
Oxidant-induced DNA damage of target cells.
I. Schraufstätter (1988)
Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster.
A. Nemmar (2001)
Health effects of exposure to diesel exhaust particles.
R. Mcclellan (1987)
8-hydroxy-2'-deoxyguanosine, a major mutagenic oxidative DNA lesion, and DNA strand breaks in nasal respiratory epithelium of children exposed to urban pollution.
L. Calderón‐Garcidueñas (1999)
Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers.
S. Loft (1999)
The quartz hazard: a variable entity.
K. Donaldson (1998)
SHORT COMMUNICATION: Glutathione modulates the formation of 8-hydroxydeoxyguannosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres
P. Howden (1996)
An overview of the relationship between oxidative stress and chemical carcinogenesis.
M. Trush (1991)
Cytogenetic damage and occupational exposure
R. C. Sobti (1991)
Inhaled crocidolite mutagenicity in lung DNA.
B. Rihn (2000)
DNA single-strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum.
A. Fornace (1976)
Ambient Particulate Matter Induces Oxidative Dna Damage in Lung Epithelial Cells
A. Knaapen (2000)
The Detection of Chemical Mutagens with Enteric Bacteria
B. Ames (1971)
Induction of sister
C. Hornberg (1998)
Increased Incidence of DNA Double-strand Breaks and Anti-ds DNA Antibodies in Blood of Workers Occupationally Exposed to Asbestos
B. Marczynski (1994)
DNA damage and inflammation in the rat quartz model
J. Bruch (2000)
Neutrophils cause oxidative DNA damage in alveolar epithelial cells.
A. Knaapen (1999)
Lung tumor induction upon long-term low-level inhalation of crystalline silica.
H. Muhle (1989)
Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles
A. Kane (2000)
Occupational and Environmental Factors Enhancing the Genotoxicity of Asbestos
Q. Rahman (2000)
The Comet Assay (Single-Cell Gel Test)
G. Speit (1999)
Effects of particle exposure and particle-elicited inflammatory cells on mutation in rat alveolar epithelial cells.
K. Driscoll (1997)
Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells.
O. Ostling (1984)
Genotoxicity of coke-oven and urban air particulate matter in in vitro acellular assays coupled with 32P-postlabeling and HPLC analysis of DNA adducts.
B. Binková (1998)
Mutagenic activity of airborne particulates at non-industrial locations.
G. Alink (1983)
Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica.
C. Johnston (2000)
Cell signaling pathways elicited by asbestos.
B. Mossman (1997)
Role of oxyradicals in mutagenicity and DNA damage induced by crocidolite asbestos in mammalian cells.
A. Xu (1999)
Genetics of Human Cancer
R. Harris (1977)
A simple technique for quantitation of low levels of DNA damage in individual cells.
N. Singh (1988)
Formation of 8-hydroxydeoxyguanosine by asbestos and man made mineral fibres.
P. Leanderson (1988)
Formation of DNA adducts in rat lung following chronic inhalation of diesel emissions, carbon black and titanium dioxide particles.
J. Gallagher (1994)
32P-postlabeling test for covalent DNA binding of chemicals in vivo: application to a variety of aromatic carcinogens and methylating agents.
M. V. Reddy (1984)
DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe
A. J. Ghio (1994)
Asbestos and glass fibres in bacterial mutation tests.
M. Chamberlain (1977)
Use of in-vitro genotoxicity and cell transformation assays to evaluate the potential carcinogenicity of fibres.
Jaurand Mc (1996)
In vitro and in vivo effects of ambient particulates
R. Schins (2000)
Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and apoptosis in mesothelial cells.
W. Liu (2000)
Genetic toxicology data in the evaluation of potential human environmental carcinogens.
M. Waters (1999)
Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos.
H. Fung (1997)
Pulmonary inflammatory, chemokine, and mutagenic responses in rats after subchronic inhalation of carbon black.
K. Driscoll (1996)
Crocidolite asbestos increased 8-hydroxydeoxyguanosine levels in cellular DNA of a human promyelocytic leukemia cell line, HL60.
T. Takeuchi (1994)
Oxidative DNA damage by crystalline silica.
L. Daniel (1993)
Role of Mitogen-Activated Protein Kinases, Early Response Protooncogenes, and Activator Protein-1 in Cell Signaling by Asbestos
B. Mossman (2000)
Genotoxic activity of nitrosated coal dust extract in mammalian systems.
J. Tucker (1984)
Nuclear Factor Kappa-B Activation by Particles and Fibers
R. Schins (2000)
Tumor suppressor genes
C. Marshall (1991)
DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe 3+
A J Ghio (1994)
Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years.
K. P. Lee (1985)
Lung particle overload: implications for occupational exposures to particles.
G. Oberdörster (1995)
The maximum tolerated dose for inhalation bioassays: toxicity vs overload.
P. Morrow (1996)
Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings.
M. Yegles (1995)
Silica radical-induced DNA damage and lipid peroxidation.
X. Shi (1994)
Diesel and gasoline exhausts and some nitroarenes
Use of genotoxicity and cell transformation assays to evaluate potential carcinogenicity of fibres
M. C. Jaurand (1996)
The role of free radicals in asbestosinduced diseases
D. W. Kamp (1992)
Endogenous mutagens and the causes of aging and cancer.
B. Ames (1991)
Transgenic systems for in vivo mutation analysis.
G. Provost (1993)
8-Hydroxyguanosine formed in human lung tissues and the association with diesel exhaust particles.
H. Tokiwa (1999)
Phospholipid surfactant adsorption by respirable quartz and in vitro expression of cytotoxicity and DNA damage.
X. Liu (1998)
Mechanisms of fiber-induced genotoxicity.
M. Jaurand (1997)
Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles.
T. Ichinose (1997)
DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution.
L. Calderón‐Garcidueñas (1996)
Toxicity of fibers and particles
H. Greim (2001)
Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.
K. Donaldson (1988)
Toxic and carcinogenic effects of solid particles in the respiratory tract
D. Dungworth (1994)
Particles, inflammation and respiratory tract carcinogenesis.
P. Borm (1996)
Correlative genotoxicity studies of airborne particles in Salmonella typhimurium and cultured human lymphocytes.
G. Krishna (1984)
Does occupational exposure to silica cause lung cancer?
D. Goldsmith (1982)
The role of free radicals in asbestos-induced diseases.
D. Kamp (1992)
The maximum tolerated dose for inhalation bioassays: toxicity vs overload.
P. Morrow (1996)
Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies
T. Hei (2000)
Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay.
P. L. Olive (1990)
The use of shuttle vectors for mutation analysis in transgenic mice and rats.
M. Dycaico (1994)
In vitro effects of coal fly ashes: hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells.
J. V. van Maanen (1999)
DNA Damage and Inflammation in the Rat Quartz Model: Differences in Inflammatory Response and Formation of Oxidative DNA Adducts to High and Low Dose of DQ12 Quartz
J. Bruch (2000)
The future of transgenic mutation models: Introduction to the panel discussion
E. Zeiger (1998)
Oxidative DNA damage in peripheral blood lymphocytes of coal workers
R. Schins (1995)
Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite.
S. Faux (1994)
Mutagens and carcinogens in size-classified air particulates of a northern Italian town.
S. Monarca (1997)
Genotoxicity and chronic health effects of automobile exhaust: a study on the traffic policemen in the city of Lanzhou.
X. Zhao (1998)
Free radical activity of PM10: iron-mediated generation of hydroxyl radicals.
K. Donaldson (1997)
Assessment of the oxidant acitvity of ambient particulate matter
T. Shi (2001)
Detection of surface free radical activity of respirable industrial fibres using supercoiled phi X174 RF1 plasmid DNA.
P. Gilmour (1995)
Oxidative DNA damage induced by silica in vivo.
Y. Yamano (1995)
Genotoxicity of diesel-exhaust particles dispersed in simulated pulmonary surfactant.
M. Keane (1991)
Characterising mutagenesis in the HPRT gene of rat alveolar epithelial cells
K. E. Driscoll (1995)
The role of catalytic iron in asbestos induced lipid peroxidation and DNA-strand breakage in C3H10T1/2 cells.
C. J. Turver (1987)
The use of short-and medium-term tests for carcinogens and data on genetic effects in carcinogenic hazard evaluation. Consensus report.
J. Rice (1999)
In vitro cytogenetic assays for the detection of mitotic aneuploidy by particulate pollutants.
W. Hadnagy (1991)
Silica, Some Silicates, Coal Dust and Para-aramid Fibrils. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 68
B. Raju (2004)
Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges, and cancer risk assessment.
J. Tucker (1996)
This paper is referenced by
Effect of Asbestos-Containing Products with Harmless Treatment on the Lungs
Yasuo Morimoto (2009)
Inhalation of Nanomaterials: Short Overview of the Local and Systemic Effects
P. Hoet (2007)
Macrophages detoxify the genotoxic and cytotoxic effects of surgical cobalt chrome alloy particles but not quartz particles on human cells in vitro.
I. Papageorgiou (2008)
Inhibitory effect of silver nanoparticles mediated by atmospheric pressure air cold plasma jet against dermatophyte fungi.
Salama A. Ouf (2015)
Evaluation of genotoxicity of multi-walled carbon nanotubes in a battery of in vitro and in vivo assays.
M. Ema (2012)
Toxicity of Transition Metal Oxide Nanoparticles: Recent Insights from in vitro Studies
Y. Huang (2010)
Genotoxicity of engineered nanomaterials: A critical review
L. Gonzalez (2008)
Increased micronucleus frequencies in surrogate and target cells from workers exposed to crystalline silica-containing dust.
G. C. Demircigil (2010)
Air pollution and cancer: biomarker studies in human populations.
P. Vineis (2005)
Biological effects of metal-on-metal hip replacements
M. Bhamra (2006)
Mutagenicity of diesel exhaust particles mediated by cell-particle interaction in mammalian cells.
Lingzhi Bao (2007)
Inflammasome Activation by Pathogenic Crystals and Particles
F. Re (2011)
Neoplasms of the Pleura
S. Hammar (2008)
Effects of Occupational Silica Exposure on OXIDATIVE Stress and Immune System Parameters in Ceramic Workers in TURKEY
Hatice Gul Anlar (2017)
Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.
J. Goodman (2014)
Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response
A. Van der Meeren (2008)
The role of the surface chemistry of CoCr alloy particles in the phagocytosis and DNA damage of fibroblast cells.
A. C. Lewis (2007)
A Lab-based Study for the Generation and Characterization of Particle Emission from Composite Materials Containing Carbon Nanotubes
J. Kang (2016)
Does the exposure to salinity variations and water dispersible carbon nanotubes induce oxidative stress in Hediste diversicolor?
L. De Marchi (2018)
Chapter Three – Genotoxicity of Polycyclic Aromatic Hydrocarbon Metabolites: Radical Cations and Ketones
Sushmita Sen (2013)
Evaluation of Direct-Oxidative DNA Damage on Human Lung Epithelial Cells Exposed to Urban Airborne Particulate Matter
Delia Cavallo (2008)
Effect of Surface Chemistry on the Immune Responses and Cellular Interactions of Porous Silicon Nanoparticles
M. Shahbazi (2015)
OPINION ON SAFETY OF NANOMATERIALS IN COSMETIC PRODUCTS
Claire Chambers (2007)
Genotoxic Effects of Particles
R. Schins (2006)
Exploring the Damage Limitation Possibilities of Mineral Fibres for Future Integrated Solutions: An in Vitro Study
F. Gabbanelli (2003)
Genetic effects of air pollutants: insights from human biomonitoring studies.
R. Crebelli (2009)
Methodological considerations for using umu assay to assess photo-genotoxicity of engineered nanoparticles.
Denisa Cupi (2016)
Genotoxicity of Nanoparticles
Amaya Azqueta (2014)
Modélisation génétique de l'oncogenèse mésothéliale induite par les fibres minérales
C. Boulangé-Lecomte (2004)
Metal and Anion Composition of Two Biopolymeric Chemical Stabilizers and Toxicity Risk Implication for the Environment
P. P. Ndibewu (2010)
Chemical characteristics and mutagenic activity of PM10 in Torino, a northern Italian city.
G. Gilli (2007)
15.05 – Alveolar Epithelium in Lung Toxicology
L. Chang (2018)See more