Chrysotile effects on human lung cell carcinoma in culture: 3-D reconstruction and DNA quantification by image analysis

Cortez, Beatriz Araujo; Machado-Santelli, Gláucia Maria

doi:10.1186/1471-2407-8-181

Cited by 29 publications

(37 citation statements)

References 26 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mitotic spindle damage with a predominantly multipolar phenotype and aneuploidy have also been observed following in vitro treatment with 0.25 μg/mL of the potent occupational carcinogen, chrysotile asbestos [80]. The ability of asbestos fibers to induce aneuploidy in vitro is highly correlated with the ability to induce mesotheliomas in vivo; this provides data supporting the importance of aneuploidy in carcinogenesis due to particulates with high aspect ratios [81].…”

Section: Discussionsupporting

confidence: 55%

“…The affinity for the DNA as well as the similarity of the carbon nanotube size and physical properties to the cellular microtubules [39,63] may enhance the potential for aneuploidy. By contrast, asbestos fibers have a low affinity for the DNA but the larger asbestos fibers can physically interfere with the mitotic spindle [80]. The incorporation of the nanotubes into the centrosomal structure as well as the integration of the carbon nanotubes with the microtubules in the mitotic spindle may exert physical forces that fragment the centrosome, disrupt the mitotic spindle, and induce errors in chromosome number that are possible at the current levels of exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Similarities of the carbon nanotube to microtubules noted by Pampaloni et al, 2008 may explain the interaction with the centrosome and mitotic spindles rather than the physical interference of the spindle that occurs with fibers such as asbestos [80]. The affinity for the DNA as well as the similarity of the carbon nanotube size and physical properties to the cellular microtubules [39,63] may enhance the potential for aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

148

123

View full text Add to dashboard Cite

Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 μg/cm 2 single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 μg/cm 2 SWCNT. Three- Conflict of interest statementThe authors declare that there are no conflicts of interest. Appendix A. Supplementary dataSupplementary data associated with this article can be found, in the online version, at doi:10.1016/j.mrgentox.2011.11.017. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24 h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

148

123

View full text Add to dashboard Cite

show abstract

“…Mitotic spindle damage and aneuploidy have also been observed following in vitro treatment with 0.25 mg/ml of the potent occupational carcinogen, chrysotile asbestos [Cortez and Machado-Santelli, 2008]. The dose of the chrysotile used in the in vitro studies was 10-fold higher than the lowest dose of SWCNT that induced similar damage.…”

Section: Discussionmentioning

confidence: 94%

“…Our results suggest that SWCNT may indeed exert genotoxic effects due to their resistance to biological clearance, in addition to specific interactions with cellular components that alters the orderly progression of cell division. The nanotube bundles are similar to the size of the microtubules , and may be incorporated into the mitotic spindle rather than the physical interference of the spindle that occurs with the larger asbestos fibers [Cortez and Machado-Santelli, 2008]. Centrosome fragmentation, mitotic spindle disruption, and aneuploidy are characteristics Environmental and Molecular Mutagenesis.…”

Section: Discussionmentioning

confidence: 99%

Induction of aneuploidy by single‐walled carbon nanotubes

Sargent

Shvedova

Hubbs

et al. 2009

Environ and Mol Mutagen

155

152

View full text Add to dashboard Cite

Engineered carbon nanotubes are newly emerging manufactured particles with potential applications in electronics, computers, aerospace, and medicine. The low density and small size of these biologically persistent particles makes respiratory exposures to workers likely during the production or use of commercial products. The narrow diameter and great length of single-walled carbon nanotubes (SWCNT) suggest the potential to interact with critical biological structures. To examine the potential of nanotubes to induce genetic damage in normal lung cells, cultured primary and immortalized human airway epithelial cells were exposed to SWCNT or a positive control, vanadium pentoxide. After 24 hr of exposure to either SWCNT or vanadium pentoxide, fragmented centrosomes, multiple mitotic spindle poles, anaphase bridges, and aneuploid chromosome number were observed. Confocal microscopy demonstrated nanotubes within the nucleus that were in association with cellular and mitotic tubulin as well as the chromatin. Our results are the first to report disruption of the mitotic spindle by SWCNT. The nanotube bundles are similar to the size of microtubules that form the mitotic spindle and may be incorporated into the mitotic spindle apparatus.

show abstract

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p₆‐histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy

Parihar

Dube

2022

Luminescence

View full text Add to dashboard Cite

We have explored the intracellular cell organelle's structural alterations after photodynamic treatment with chlorin p6‐histamine conjugate (Cp6‐his) in human oral cancer cells. Herein, the cells were treated with Cp6‐his (10 μm) and counterstained with organelle‐specific fluorescence probes to find the site of intracellular localization using confocal microscopy. For photodynamic therapy (PDT), the cells were exposed to ~30 kJ/m2 red light (660 ± 20 nm) to induce ~90% cytotoxicity. We used the three‐dimensional (3D) image reconstruction approach to analyze the photodynamic damage to cell organelles. The result showed that Cp6‐his localized mainly in the endoplasmic reticulum (ER) and lysosomes but not in mitochondria and Golgi apparatus (GA). The 3D model revealed that in necrotic cells, PDT led to extensive fragmentation of ER and fragmentation and swelling of GA as well. Results suggest that the indirect damage to GA occurred due to loss of connection between ER and GA. Moreover, in damaged cells with no sign of necrosis, the perinuclear ER appeared condensed and surrounded by several small clumps at the peripheral region of the cell, and the GA was observed to form a single condensed structure. Since these structural changes were associated with apoptotic cell death, it is suggested that the necrotic and apoptotic death induced by PDT with Cp6‐his is determined by the severity of damage to ER and indirect damage to GA. The results suggest that the indirect damage to cell organelle apart from the sites of photosensitizer localization and the severity of damage at the organelle level contribute significantly to the mode of cell death in PDT.

show abstract

Chrysotile effects on human lung cell carcinoma in culture: 3-D reconstruction and DNA quantification by image analysis

Cited by 29 publications

References 26 publications

Single-walled carbon nanotube-induced mitotic disruption

Single-walled carbon nanotube-induced mitotic disruption

Induction of aneuploidy by single‐walled carbon nanotubes

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p₆‐histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy

Contact Info

Product

Resources

About

Chrysotile effects on human lung cell carcinoma in culture: 3-D reconstruction and DNA quantification by image analysis

Cited by 29 publications

References 26 publications

Single-walled carbon nanotube-induced mitotic disruption

Single-walled carbon nanotube-induced mitotic disruption

Induction of aneuploidy by single‐walled carbon nanotubes

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p6‐histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy

Contact Info

Product

Resources

About

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p₆‐histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy