Micronucleus assay for mouse alveolar Type II and Clara cells

Lindberg, Hanna; Falck, Ghita C.-M.; Catalán, Julia; Santonen, Tiina; Norppa, Hannu

doi:10.1002/em.20520

Cited by 16 publications

(10 citation statements)

References 50 publications

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“…Another study revealed that TiO 2 nanoparticles could be slightly genotoxic, i.e. affecting DNA [21].…”

Section: Data From Research and Animal Studies On Nanomaterialsmentioning

confidence: 99%

Environmental and Health Safety Considerations of Nanotechnology: Nano Safety

Osman

2019

BJSTR

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Nanotechnologies are being spoken of as the driving force behind the new industrial revolution. The mass production of these nano materials and their applications mean a dramatic increase of workers dealing with Engineered Nano Materials ENM and becoming possibly exposed to resulting hazardous effects and increased environmental burden of the environment due to the leaks of these materials from industrial processes. It is hence essential to consider the importance of ENM safety and their new applications and understand that, it is important for these materials and products to be safe to enable successful promotion of nanotechnology for useful applications. The aim of this article is to review the impact of the ENM on both human and environment. Also, the risk and the risk assessment of the ENM we deal with.

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“…Another study revealed that TiO 2 nanoparticles could be slightly genotoxic, i.e. affecting DNA [21].…”

Section: Data From Research and Animal Studies On Nanomaterialsmentioning

confidence: 99%

Environmental and Health Safety Considerations of Nanotechnology: Nano Safety

Osman

2019

BJSTR

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“…It was also planned to conduct a micronucleus assay on lung cells, but concerted and prolonged attempts to validate such an assay on cells from mouse lung were unsuccessful, so this part of the study design was eventually abandoned. While these efforts were in progress, a technique for conducting micronucleus studies on mouse lung cells was successfully devised and used to follow the effect of exposure to ethylene oxide 15 .…”

Section: Introductionmentioning

confidence: 99%

First Steps Towards an Understanding of a Mode of Carcinogenic Action for Vanadium Pentoxide

Schuler¹,

Chevalier²,

Merker³

et al. 2011

J Toxicol Pathol

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Inhalation of vanadium pentoxide clearly increases the incidence of alveolar/bronchiolar neoplasms in male and female B6C3F1 mice at all concentrations tested (1, 2 or 4 mg/m3), whereas responses in F344/N rats was, at most, ambiguous. While vanadium pentoxide is mutagenic in vitro and possibly in vivo in mice, this does not explain the species or site specificity of the neoplastic response. A nose-only inhalation study was conducted in female B6C3F1 mice (0, 0.25, 1 and 4 mg/m3, 6 h/day for 16 days) to explore histopathological, biochemical (α-tocopherol, glutathione and F2-isoprostane) and genetic (comet assays and 9 specific DNA-oxo-adducts) changes in the lungs. No treatment related histopathology was observed at 0.25 mg/m3. At 1 and 4 mg/m3, exposure-dependent increases were observed in lung weight, alveolar histiocytosis, sub-acute alveolitis and/or granulocytic infiltration and a generally time-dependent increased cell proliferation rate of histiocytes. Glutathione was slightly increased, whereas there were no consistent changes in α-tocopherol or 8-isoprostane F2α. There was no evidence for DNA strand breakage in lung or BAL cells, but there was an increase in 8-oxodGuo DNA lesions that could have been due to vanadium pentoxide induction of the lesions or inhibition of repair of spontaneous lesions. Thus, earlier reports of histopathological changes in the lungs after inhalation of vanadium pentoxide were confirmed, but no evidence has yet emerged for a genotoxic mode of action. Evidence is weak for oxidative stress playing any role in lung carcinogenesis at the lowest effective concentrations of vanadium pentoxide.

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“…For example, chromosomal aberrations and reciprocal translocations have also been observed in the peripheral lymphocytes of B6C3F 1 mice (Donner et al, 2010). In addition, increases in the frequency of micronucleated alveolar type II cells and Clara cells were observed in mice following inhalation of 630 mg/m 3 EO for 4 h (Lindberg et al, 2010).…”

mentioning

confidence: 97%

Temporal Changes in K-ras Mutant Fraction in Lung Tissue of Big Blue B6C3F1 Mice Exposed to Ethylene Oxide

Parsons

Manjanatha

Myers

et al. 2013

Toxicological Sciences

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Ethylene oxide (EO) is a genotoxicant and a mouse lung carcinogen, but whether EO is carcinogenic through a mutagenic mode of action remains unclear. To investigate this question, 8-week-old male Big Blue B6C3F₁ mice (10 mice/group) were exposed to EO by inhalation-6 h/day, 5 days/week for 4 weeks (0, 10, 50, 100, or 200 ppm EO) and 8 or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples were analyzed for levels of 3 K-ras codon 12 mutations (GGT→GAT, GGT→GTT, and GGT→TGT) using ACB-PCR. No measureable level of K-ras codon 12 TGT mutation was detected (ie, all lung mutant fractions [MFs] ≤ 10⁻⁵). Four weeks of inhalation of 100 ppm EO caused a significant increase in K-ras codon 12 GGT→GTT MF relative to controls, whereas 50, 100, and 200 ppm EO caused significant increases in K-ras codon 12 GGT→GAT MF. In addition, significant inverse correlations were observed between K-ras codon 12 GGT→GTT MF and cII mutant frequency in the lungs of the same mice exposed to 50, 100, or 200 ppm EO for 4 weeks. Surprisingly, 8 weeks of exposure to 100 and 200 ppm EO caused significant decreases in K-ras MFs relative to controls. Thus, the changes in K-ras MF as a function of cumulative EO dose were nonmonotonic and were consistent with EO causing early amplification of preexisting K-ras mutations, rather than induction of K-ras mutation through genotoxicity at codon 12. The possibility that these changes reflect K-ras mutant cell selection under varying degrees of oxidative stress is discussed.

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Micronucleus assay for mouse alveolar Type II and Clara cells

Cited by 16 publications

References 50 publications

Environmental and Health Safety Considerations of Nanotechnology: Nano Safety

Environmental and Health Safety Considerations of Nanotechnology: Nano Safety

First Steps Towards an Understanding of a Mode of Carcinogenic Action for Vanadium Pentoxide

Temporal Changes in K-ras Mutant Fraction in Lung Tissue of Big Blue B6C3F1 Mice Exposed to Ethylene Oxide

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