Aneuploidy: a report of an ECETOC task force

Aardema, Marilyn J.; Albertini, Silvio; Arni, P.; Henderson, L.M.; Kirsch‐Volders, Micheline; Mackay, James; Sarrif, Awni M.; Stringer, D.A.; Taalman, R. D. F. M.

doi:10.1016/s1383-5742(97)00029-x

Cited by 144 publications

(77 citation statements)

References 168 publications

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“…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. Centrosome fragmentation, mitotic spindle disruption, and aneuploidy are characteristics of cancer cells and may lead to an increased risk of cancer [23,25]. Consistent with this hypothesis, research with inorganic fibers indicate that in vivo asbestos-induced mesothelioma is correlated with the ability of the fiber to cause chromosomal missegregation, not with cytotoxicity [81].…”

Section: Discussionmentioning

confidence: 80%

“…Exposure of rodents to the larger diameter MWCNT (11.3 nm) results in micronuclei in Type II epithelial cells indicating either a high level of chromosomal breakage or mitotic spindle disruption [2]. The integrity of the mitotic spindle and chromosome number are critical because mitotic spindle disruption, centrosome damage and aneuploidy may lead to a greater risk of cancer [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

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Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

148

123

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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.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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

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“…3n, 4n) is termed polyploidy, triploidy and tetraploidy, respectively. In distinction from mammals, where triploidy is usually associated with lethal to sublethal conditions (Gold and Avise, 1976;Aardema et al, 1998), in lower vertebrates, triploids are more viable and have been observed in hybrids between unisexual and bisexual species of fish, amphibians and reptiles (Thorgaard and Gall, 1979). Interest in the potential use of triploids in fish culture has been based on the assumption that these fish are in general sterile.…”

mentioning

confidence: 99%

Micronucleus occurrence in diploid and triploid rainbow trout (Oncorhynchus mykiss Walbaum)

Strunjak‐Perović¹,

Čož‐Rakovac²,

Popović³

2003

Vet. Med. - Czech

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ABSTRACT:The aim of the study was to observe the influence of different ploidy levels in fish on micronucleus occurrence. Twenty minutes a�er fertilization, one group of rainbow trout eggs was exposed to water temperatures of 26°C in duration of 20 minutes to induce triploidy. Second group was kept in water temperature of 10°C, which is optimal for development of rainbow trout. The frequency of micronucleated erythrocytes was determined in the peripheral circulation of rainbow trout 67 days (following absorption of the yolk -swim-up stage) and 128 days (fry stage) post fertilization. There was a significant difference (P < 0.001) between frequency of micronucleated erythrocytes of diploid (1.10 ± 0.96‰) and triploid (2.41 ± 1.28‰) fish at swim-up stage. Increased mean values of micronucleus in diploid (1.80 ± 1.57‰) and triploid (5.92 ± 3.80‰) fry were also recorded.

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“…(Nersesyan et al, 2006) concluded that females with PCOS have increased chromosomal aberrations (CAs) level in lymphocytes which is a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer and therefore substitute chromosomal aberrations as cancer risk biomarkers (Aardema et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Our findings suggest that there is genetic instability in peripheral blood lymphocytes of women with polycystic ovarian syndrome. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer and therefore substitute chromosomal aberrations as cancer risk biomarkers (Aardema et al, 1998). Women with PCOS have a nearly 3 times increased risk for developing endometrial cancer, the association between PCOS and endometrial cancer involves prolonged endometrial exposure to unopposed estrogen by cyclic progesterone due to anovulation (Tokmak et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome

Sekar¹,

Nair²,

Francis³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value (45.9°) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

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Aneuploidy: a report of an ECETOC task force

Cited by 144 publications

References 168 publications

Single-walled carbon nanotube-induced mitotic disruption

Single-walled carbon nanotube-induced mitotic disruption

Micronucleus occurrence in diploid and triploid rainbow trout (Oncorhynchus mykiss Walbaum)

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome

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