Inhaled Crocidolite Mutagenicity in Lung DNA

Rihn, Bertrand; Coulais, Catherine; Kauffer, E.; Bottin, M.C.; Martin, Patrick; Yvon, François; Vigneron, J. C.; Binet, Stéphane; Monhoven, Nathalie; Steiblen, Guy; Keith, Gérard

doi:10.2307/3454353

Cited by 9 publications

(7 citation statements)

References 5 publications

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“…Similar findings were recently shown by Unfried et al,6 using intraperitoneal injection of asbestos in this transgenic rat model. Specific mutational analysis in both studies demonstrated a mutagenicity pattern involving G to T transversions, which could possibly be explained by the enhanced 8‐OHdG formation as observed for both DEP and asbestos in vitro or in vivo 80, 81, 86, 95. Earlier work by Driscoll and co‐workers69 showed enhanced HPRT‐mutagenicity in alveolar epithelial cells obtained from rats that were exposed to CB or to silica but only in those conditions that resulted in a significant inflammation in the animals.…”

Section: Mechanisms Of Particle Induced Lung Neoplasmsmentioning

confidence: 84%

Inhaled particles and lung cancer. Part A: Mechanisms

Knaapen

Borm

Albrecht

et al. 2004

Intl Journal of Cancer

557

334

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Both occupational and environmental exposure to particles is associated with an increased risk of lung cancer. Particles are thought to impact on genotoxicity as well as on cell proliferation via their ability to generate oxidants such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). For mechanistic purposes, one should discriminate between a) the oxidant-generating properties of particles themselves (i.e., acellular), which are mostly determined by the physicochemical characteristics of the particle surface, and b) the ability of particles to stimulate cellular oxidant generation. Cellular ROS/RNS can be generated by various mechanisms, including particle-related mitochondrial activation or NAD(P)H-oxidase enzymes. In addition, since particles can induce an inflammatory response, a further subdivision needs to be made between primary (i.e., particle-driven) and secondary (i.e., inflammation-driven) formation of oxidants. Particles may also affect genotoxicity by their ability to carry surface-adsorbed carcinogenic components into the lung. Each of these pathways can impact on genotoxicity and proliferation, as well as on feedback mechanisms involving DNA repair or apoptosis. Although abundant evidence suggests that ROS/RNS mediate particle-induced genotoxicity and mutagenesis, little information is available towards the subsequent steps leading to neoplastic changes. Additionally, 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. In this respect, transgenic and gene knockout animal models may provide a useful tool. Such studies should also include further assessment of the relative contributions of primary (inflammation-independent) and secondary (inflammation-driven) pathways.

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Section: Mechanisms Of Particle Induced Lung Neoplasmsmentioning

confidence: 84%

Inhaled particles and lung cancer. Part A: Mechanisms

Knaapen

Borm

Albrecht

et al. 2004

Intl Journal of Cancer

557

334

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“…Although the use of asbestos fibers has been banned in most industrialized countries, fibers are still a major environmental and occupational health concern. Asbestos has been identified as a known human mutagen and carcinogen [1,2], producing several thousands of cancers each year. In France alone, asbestos is responsible for approximately 2000 new cases of bronchogenic carcinomas and mesotheliomas [3].…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression in mesothelioma

et al. 2000

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To investigate the molecular events controlling malignant transformation of human pleural cells, we compared constitutive gene expression of mesothelioma cells to that of pleural cells. Using cDNA microarray and high-density filter array, we assessed expression levels of s 6500 genes. Most of the highly expressed transcripts were common to both cell lines and included genes associated with stress response and DNA repair, outcomes consistent with the radio-and chemo-resistance of mesothelioma. Interestingly, of the fewer than 300 genes that differed between cell lines, most functioned in (i) macromolecule stability, (ii) cell adhesion and recognition, (iii) cell migration (invasiveness), and (iv) extended cell division. Expression levels of several of these genes were confirmed by RT-PCR and could be useful as diagnostic markers of human mesothelioma. ß

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“…Mutagenic activity was detected in the lung of Big Blue ® mice after inhalation [41]. As expected, clearly no systemic effects in the bone marrow could be observed in the mouse micronucleus test [4].…”

Section: Resultsmentioning

confidence: 92%

Untitled

et al. 2005

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As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects.

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Inhaled Crocidolite Mutagenicity in Lung DNA

Cited by 9 publications

References 5 publications

Inhaled particles and lung cancer. Part A: Mechanisms

Inhaled particles and lung cancer. Part A: Mechanisms

Differential gene expression in mesothelioma

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