17 research outputs found
Infant birth outcomes are associated with DNA damage biomarkers as measured by the cytokinesis block micronucleus cytome assay: the DADHI study
Infant birth outcomes are associated with DNA damage biomarkers as measured by the cytokinesis block micronucleus cytome assay: the DADHI study
Accumulation of DNA damage in the first 1000 days may increase risk of accelerated ageing and degenerative diseases in adult life such as cancers. The extent of DNA damage in infants and the correlation of maternal factors during pregnancy with neonate birth outcomes and DNA damage is not known in infants born in Australia. Therefore, we performed a prospective cohort study to collect data on DNA damage in lymphocytes of Australian infants (aged 0, 3 and 6 months), using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay. The study also explored correlation of CBMN-Cyt biomarkers with infant birth outcomes and maternal anthropometric and lifestyle variables. Peripheral blood lymphocytes were isolated from the infants at birth (cord blood) (n = 82), 3 months (n = 64) and 6 months (n = 53) after birth. DNA damage biomarkers measured ex vivo in binucleated lymphocytes (BNC) included: micronuclei (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUD). Apoptotic and necrotic lymphocytes were also scored and nuclear division index (NDI) was measured using the frequency of mono-, bi- and multinucleated lymphocyte. MN and NBUD were also scored in mononucleated lymphocytes (MNC). The mean (± SD) frequency of MN, NPB and NBUD in BNCs at birth was 2.0 (± 1.2), 5.8 (± 3.7) and 11.1 (± 5.7) per 1000 BNC, respectively, and tended to decrease significantly at 3 months (P P P P P P n = 48 at birth, 48 at 3 months and 39 at 6 months). None of the CBMN cytome biomarkers measured at birth was associated with maternal smoking status, alcohol and folic acid intake during pregnancy. The mean gestation age correlated positively with MN (r = 0.38, P = 0.006), NPB (r = 0.30, P = 0.03) and negatively with NDI (r = −0.29, P = 0.03). Infant birth weight associated positively with MN, NPB and NBUD in cord blood (r = 0.24, P = 0.08" r = 0.32, P = 0.02" r = 0.28, P = 0.04, respectively), birth length associated positively with NPB (r = 0.32, P = 0.02) and NBUD (r = 0.27, P = 0.04) while head circumference associated negatively with apoptotic cells (r = −0.27, P = 0.06). APGAR score at 1 and 5 min after birth associated positively with NDI at birth (r = 0.3, P = 0.05, r = 0.28, P = 0.06, respectively). Mother's weight and body mass index (BMI) recorded at the time of recruitment associated positively with NPB (r = 0.38, P = 0.006, r = 0.32, P = 0.02, respectively) and negatively with APGAR score at 5 min (r = −0.25, P = 0.07). The significant positive associations of infant birth weight and length and maternal BMI with CBMN-Cyt biomarkers suggest the possibility of a genotoxic effect of metabolic processes that promote excessive growth and high BMI
Workers exposed to wood dust have an increased micronucleus frequency in nasal and buccal cells: results from a pilot study.
Wood dust is recognised as a human carcinogen, based on the strong association of wood dust exposure and the elevated risk of malignant tumours of the nasal cavity and paranasal sinuses [sino-nasal cancer (SNC)]. The study aimed to assess genetic damage in workers exposed to wood dust using biomarkers in both buccal and nasal cells that reflect genome instability events, cellular proliferation and cell death frequencies. Nasal and buccal epithelial cells were collected from 31 parquet layers, installers, carpenters and furniture workers (exposed group) and 19 non-exposed workers located in Switzerland. Micronucleus (MN) frequencies were scored in nasal and buccal cells collected among woodworkers. Other nuclear anomalies in buccal cells were measured through the use of the buccal micronucleus cytome assay. MN frequencies in nasal and buccal cells were significantly higher in the exposed group compared to the non-exposed group; odds ratio for nasal cells 3.1 [95% confidence interval (CI) 1.8-5.1] and buccal cells 1.8 (95% CI 1.3-2.4). The exposed group had higher frequencies of cells with nuclear buds, karyorrhectic, pyknotic, karyolytic cells and a decrease in the frequency of basal, binucleated and condensed cells compared to the non-exposed group. Our study confirms that woodworkers have an elevated risk for chromosomal instability in cells of the aerodigestive tract. The MN assay in nasal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk. Future studies should seek to standardise the protocol for MN frequency in nasal cells similar to that for MN in buccal cells
Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer’s Disease
The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD/MCI pathogenesis is unclear. This study compared the metabolomic and proteomic signature of plasma from cognitively normal (CN) and dementia patients diagnosed with MCI or AD, to identify specific cellular pathways and new biomarkers altered with the progression of the disease. We analysed 80 plasma samples from individuals with MCI or AD, as well as age- and gender-matched CN individuals, by utilising mass spectrometry methods and data analyses that included combined pathway analysis and model predictions. Several proteins clearly identified AD from the MCI and CN groups and included plasma actins, mannan-binding lectin serine protease 1, serum amyloid A2, fibronectin and extracellular matrix protein 1 and Keratin 9. The integrated pathway analysis showed various metabolic pathways were affected in AD, such as the arginine, alanine, aspartate, glutamate and pyruvate metabolism pathways. Therefore, our multi-omics approach identified novel plasma biomarkers for the MCI and AD groups, identified changes in metabolic processes, and may form the basis of a biomarker panel for stratifying dementia participants in future clinical trials
DNA Melting and Genotoxicity Induced by Silver Nanoparticles and Graphene
We
have revealed a connection between DNA-nanoparticle (NP) binding
and <i>in vitro</i> DNA damage induced by citrate- and branched
polyethylenimine-coated silver nanoparticles (c-AgNPs and b-AgNPs)
as well as graphene oxide (GO) nanosheets. All three types of nanostructures
triggered an early onset of DNA melting, where the extent of the melting
point shift depends upon both the type and concentration of the NPs.
Specifically, at a DNA/NP weight ratio of 1.1/1, the melting temperature
of lambda DNA dropped from 94 °C down to 76 °C, 60 °C,
and room temperature for GO, c-AgNPs and b-AgNPs, respectively. Consistently,
dynamic light scattering revealed that the largest changes in DNA
hydrodynamic size were also associated with the binding of b-AgNPs.
Upon introduction to cells, b-AgNPs also exhibited the highest cytotoxicity,
at the half-maximal inhibitory (IC<sub>50</sub>) concentrations of
3.2, 2.9, and 5.2 mg/L for B and T-lymphocyte cell lines and primary
lymphocytes, compared to the values of 13.4, 12.2, and 12.5 mg/L for
c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets, respectively.
At cytotoxic concentrations, all NPs elicited elevated genotoxicities
via the increased number of micronuclei in the lymphocyte cells. However,
b-AgNPs also induced micronuclei at subtoxic concentrations starting
from 0.1 mg/L, likely due to their stronger cellular adhesion and
internalization, as well as their subsequent interference with normal
DNA synthesis or chromosome segregation during the cell cycle. This
study facilitates our understanding of the effects of NP chemical
composition, surface charge, and morphology on DNA stability and genotoxicity,
with implications ranging from nanotoxicology to nanobiotechnology
and nanomedicine
‘Shut up and bill’: Workplace bullying challenges for the legal profession
Competition, work intensification and requirements for efficiency are some of the hallmarks of the modern work environment. Pressures in such settings can result in stress caused by long work hours, a lack of work–life balance and interpersonal conflict. The legal profession is prone to negative impacts due to its highly competitive environment. This, coupled with established hierarchical structures, significant power imbalances and pressure to measure work input rather than output (billable hours), can create ‘toxic’ settings. This paper reports the findings of a study of dignity and respect in the legal profession. Results indicate that many of the issues arise due to negative workplace cultures brought about and perpetuated by work practices and the leadership of the firm. Often the prevailing culture of intense competition, and a win-at-all-costs mentality, has negative repercussions for the security and standing of individuals. Those with position and power use work practices such as billable hours to push others to perform at extraordinary levels, in turn adversely affecting their well-being, quality of work life and tenure in the organisation or profession. The way forward would require a multi-pronged approach and cooperation and collaboration by the relevant stakeholders: regulators, professional associations, institutions and individuals
Inter-laboratory consistency and variability in the buccal micronucleus cytome assay depends on biomarker scored and laboratory experience: results from the HUMNxl international inter-laboratory scoring exercise
The buccal micronucleus cytome (BMNcyt) assay in uncultured exfoliated
epithelial cells from oral mucosa is widely applied in biomonitoring
human exposures to genotoxic agents and is also proposed as a suitable
test for prescreening and follow-up of precancerous oral lesions. The
main limitation of the assay is the large variability observed in the
baseline values of micronuclei (MNi) and other nuclear anomalies mainly
related to different scoring criteria. The aim of this international
collaborative study, involving laboratories with different level of
experience, was to evaluate the inter- and intra-laboratory variations
in the BMNcyt parameters, using recently implemented guidelines, in
scoring cells from the same pooled samples obtained from healthy
subjects (control group) and from cancer patients undergoing
radiotherapy (treated group). The results indicate that all laboratories
correctly discriminated samples from the two groups by a significant
increase of micronucleus (MN) and nuclear bud (NBUD) frequencies and
differentiated binucleated (BN) cells, associated with the exposure to
ionizing radiation. The experience of the laboratories was shown to play
an important role in the identification of the different cell types and
nuclear anomalies. MN frequency in differentiated mononucleated (MONO)
and BN cells showed the greatest consistency among the laboratories and
low variability was also detected in the frequencies of MONO and BN
cells. A larger variability was observed in classifying the different
cell types, indicating the subjectivity in the interpretation of some of
the scoring criteria while reproducibility of the results between
scoring sessions was very good. An inter- laboratory calibration
exercise is strongly recommended before starting studies with BMNcyt
assay involving multiple research centers