Fant 9759 publikasjoner. Viser side 292 av 391:
2013
2005
2010
2010
Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?
The comet assay is used to measure DNA damage induced by chemical and physical agents. High concentrations of test agents may cause cytotoxicity or cell death, which may give rise to false positive results in the comet assay. Systematic studies on genotoxins and cytotoxins (i.e. non-genotoxic poisons) have attempted to establish a threshold of cytotoxicity or cell death by which DNA damage results measured by the comet assay could be regarded as a false positive result. Thresholds of cytotoxicity/cell death range from 20% to 50% in various publications. Curiously, a survey of the latest literature on comet assay results from cell culture studies suggests that one-third of publications did not assess cytotoxicity or cell death. We recommend that it should be mandatory to include results from at least one type of assay on cytotoxicity, cell death or cell proliferation in publications on comet assay results. A combination of cytotoxicity (or cell death) and proliferation (or colony forming efficiency assay) is preferable in actively proliferating cells because it covers more mechanisms of action. Applying a general threshold of cytotoxicity/cell death to all types of agents may not be applicable; however, 25% compared to the concurrent negative control seems to be a good starting value to avoid false positive comet assay results. Further research is needed to establish a threshold value to distinguish between true and potentially false positive genotoxic effects detected by the comet assay.
2022
Do Carbon Nanotubes and Asbestos Fibers Exhibit Common Toxicity Mechanisms?
During the last two decades several nanoscale materials were engineered for industrial and medical applications. Among them carbon nanotubes (CNTs) are the most exploited nanomaterials with global production of around 1000 tons/year. Besides several commercial benefits of CNTs, the fiber-like structures and their bio-persistency in lung tissues raise serious concerns about the possible adverse human health effects resembling those of asbestos fibers. In this review, we present a comparative analysis between CNTs and asbestos fibers using the following four parameters: (1) fibrous needle-like shape, (2) bio-persistent nature, (3) high surface to volume ratio and (4) capacity to adsorb toxicants/pollutants on the surface. We also compare mechanisms underlying the toxicity caused by certain diameters and lengths of CNTs and asbestos fibers using downstream pathways associated with altered gene expression data from both asbestos and CNT exposure. Our results suggest that indeed certain types of CNTs are emulating asbestos fiber as far as associated toxicity is concerned.
MDPI
2022
2009
DNA repair gene polymorphisms and chromosomal aberrations in healthy, nonsmoking population
Elsevier
2021
DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations
DNA damage and unrepaired or insufficiently repaired DNA double-strand breaks as well as telomere shortening contribute to the formation of structural chromosomal aberrations (CAs). Non-specific CAs have been used in the monitoring of individuals exposed to potential carcinogenic chemicals and radiation. The frequency of CAs in peripheral blood lymphocytes (PBLs) has been associated with cancer risk and the association has also been found in incident cancer patients. CAs include chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs) and their sum CAtot. In the present study, we used data from our published genome-wide association studies (GWASs) and extracted the results for 153 DNA repair genes for 607 persons who had occupational exposure to diverse harmful substances/radiation and/or personal exposure to tobacco smoking. The analyses were conducted using linear and logistic regression models to study the association of DNA repair gene polymorphisms with CAs. Considering an arbitrary cutoff level of 5 × 10–3, 14 loci passed the threshold, and included 7 repair pathways for CTA, 4 for CSA, and 3 for CAtot; 10 SNPs were eQTLs influencing the expression of the target repair gene. For the base excision repair pathway, the implicated genes PARP1 and PARP2 encode poly(ADP-ribosyl) transferases with multiple regulatory functions. PARP1 and PARP2 have an important role in maintaining genome stability through diverse mechanisms. Other candidate genes with known roles for CSAs included GTF2H (general transcription factor IIH subunits 4 and 5), Fanconi anemia pathway genes, and PMS2, a mismatch repair gene. The present results suggest pathways with mechanistic rationale for the formation of CAs and emphasize the need to further develop techniques for measuring individual sensitivity to genotoxic exposure.
Frontiers Media S.A.
2021
2010
2017
DNA double‐strand breaks in Arctic char (Salvelinus alpinus) from Bjørnøya in the Norwegian Arctic
High levels of organochlorine contaminants (OCs) have been found in arctic char (Salvelinus alpinus) from Lake Ellasjøen, Bjørnøya (Norwegian Arctic). The aim of the present study was to investigate the potential genotoxic effect of environmental organochlorine contaminant exposure in arctic char from Ellasjøen compared with arctic char from the low‐contaminated Lake Laksvatn nearby. Blood was analyzed using agarose gel electrophoresis and image data analysis to quantify the fraction of total DNA that migrated into the gel (DNA‐FTM) as a relative measure of DNA double‐strand breaks (DSBs). Analysis by GC‐MS of muscle samples showed an average 43 times higher concentration of ΣOCs in arctic char from Ellasjøen (n = 18) compared with Laksvatn char (n = 21). Char from Lake Ellasjøen had a much higher frequency of DSBs, as measured by DNA‐FTM, than char from Lake Laksvatn. Principal component analysis and multiple linear regressions show that there was a significant positive relationship between DSBs and levels of organochlorine contaminants in the char. In addition, DSBs were less frequent in reproductively mature char than in immature char. The results suggest that organochlorine contaminants are genotoxic to arctic char.
Pergamon Press
2019
2014
2016
2024
2021
2018
Environmental contaminants are found throughout Arctic marine ecosystems, and their presence in seabirds has been
associated with toxicological responses. However, there are few studies of genotoxicity in Arctic avian wildlife. The purpose of
the present study was to quantify deoxyribonucleic acid (DNA) damage in lymphocytes of selected seabird species and to
examine whether accumulation of organohalogen contaminants (SOHCs) affects DNA damage. Blood was sampled from
common eider (Somateria mollissima), black guillemot (Cepphus grylle), black-legged kittiwake (Rissa tridactyla), glaucous gull
(Larus hyperboreus), arctic skua (Stercorarius parasiticus), and great skua (Stercorarius skua) in Kongsfjorden, Svalbard (Norway).
Contaminant concentrations found in the 6 species differed, presumably because of foraging ecology and biomagnification.
Despite large differences in contaminant concentrations, ranging from SOHCs 3.3 ng/g wet weight in the common eider to
SOHCs 895 ng/g wet weight in the great skua, there was no strong difference among the species in baseline DNA damage or
sensitivity to a genotoxic stressor (hydrogen peroxide). Baseline levels of DNA damage were low, with median values ranging
from 1.7% in the common eider to 8.6% in the great skua. There were no associations between DNA damage and contaminants
in the investigated species, suggesting that contaminant concentrations in Kongsfjorden are too low to evoke genotoxic effects,
or possibly that lymphocytes are resistant to strand breakage. Clearly, genotoxicity is a topic for future studies of Arctic seabirds
Arctic; Seabirds; Genotoxicity; Comet Assay; Persistent organic pollutants; Perfluoroalkyl substances
Pergamon Press
2018
2016
2010
2012
2010
2019