Search

Archives of toxicology 94(9), 3265-3280 (2020). doi:10.1007/s00204-020-02821-3, Published by Springer, Berlin ; Heidelberg

In the brackish water Baltic Sea, oil pollution is an ever-present and significant environmental threat mainly due to the continuously increasing volume of oil transport in the area. In this study, effects of exposure to crude oil on two common Baltic Sea species, the mussel Mytilus trossulus and the amphipod Gammarus oceanicus, were investigated. The species were exposed for various time periods (M. trossulus 4, 7, and 14 days, G. oceanicus 4 and 11 days) to three oil concentrations (0.003, 0.04, and 0.30 mg L−1 based on water measurements, nominally aimed at 0.015, 0.120, and 0.750 mg L−1) obtained by mechanical dispersion (oil droplets). Biological effects of oil exposure were examined using a battery of biomarkers consisting of enzymes of the antioxidant defense system (ADS), lipid peroxidation, phase II detoxification (glutathione S-transferase), neurotoxicity (acetylcholinesterase inhibition), and geno- and cytotoxicity (micronuclei and other nuclear deformities). In mussels, the results on biomarker responses were examined in connection with data on the tissue accumulation of polycyclic aromatic hydrocarbons (PAH). In M. trossulus, during the first 4 days of exposure the accumulation of all PAHs in the two highest exposure concentrations was high and was thereafter reduced significantly. Significant increase in ADS responses was observed in M. trossulus at 4 and 7 days of exposure. At day 14, significantly elevated levels of geno- and cytotoxicity were detected in mussels. In G. oceanicus, the ADS responses followed a similar pattern to those recorded in M. trossulus at day 4; however, in G. oceanicus, the elevated ADS response was still maintained at day 11. Conclusively, the results obtained show marked biomarker responses in both study species under conceivable, environmentally realistic oil-in-seawater concentrations during an oil spill, and in mussels, they are related to the observed tissue accumulation of oil-derived compounds.

Aim of this study was the investigation of the genotoxic properties of XLR-11 [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA-damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA-reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers.

Eruca sativa seed oil has been explored for antioxidative and antimutagenic potential. Seed oil exhibited maximum percentage inhibition of hydroxyl (93.42 %) and 2,2-diphenyl-1-picrylhydrazyl (92.02 %) radicals at the concentration of 90 μg/ml. Treatment of mice with seed oil significantly (p

In this study we compare dose distribution of photon and electron radiation in a water phantom with a frequency of occurrence of apoptotic and micronucleated cells from human bronchial BEAS-2B and lung cancer A549 cell lines. Formation of micronuclei and apoptotic like bodies were evaluated by the cytokinesis-block micronucleus test. Measurements were performed on a five depths (3-20 cm) in a water phantom. Cells were irradiated in a beam axis or beyond field. As the irradiation source, a linear accelerator was used. Results indicate discrepancy between physical dose distribution observed on different depths in a water environment and biological effects (frequency of apoptosis and micronuclei formation). This discrepancy is specially significant for cells placed outside the field during exposure to radiation. Evaluation of these effects could be useful for modeling low-dose radiation risk and for radiotherapy protocols.

Purpose Previously we have reported that DNA damage (micronuclei) observed in cells (fibroblasts) derived from the rat lung following irradiation is present in shielded regions of the lung apex following irradiation of the lung base. The present studies extend these observations to examine the effect of partial-volume irradiation of the lung base.

The induction of genotoxic effects after exposure to radiofrequency radiation represents one of the important aspects in the risk assessment of human exposure because of a close correlation between DNA damage and carcinogenesis. Most of the papers on this topic, published in peer-reviewed scientific journals, refer to experiments conducted by independent investigations who employed different experimental conditions, such as exposure characteristics, biological material examined as well as laboratory techniques. In particular, genotoxicity has been evaluated using several cytogenetic techniques, such as chromosomal aberrations, sister-chromatid exchanges, micronuclei and single-cell gel electrophoresis/ comet assay. Just a few studies were “confirmatory,” carried out adopting exactly the same experimental conditions. In this chapter the studies reported in the literature on the genotoxic potential of in vivo and in vitro exposure to radiofrequency radiation where several authors employed similar experimental conditions are compared and discussed.

Genotoxicity plays an important role for the safety evaluation of chemicals. Chromosomal aberration is one of two major end points of genotoxicity. The rodent haematopoietic cell micronucleus assay is most widely used as an in vivo test to evaluate structural and numerical chromosomal aberrations. The historical aspects of the development of the in vivo micronucleus test, the mechanism of micronucleus formation, and the characteristics of the test are reviewed. One of the limitations of the micronucleus assay is the use haematopoietic cells and it is desired to develop the genotoxic method targeted at cells other than haematopoietic cells. The micronucleus assay using cells other than bone marrow cells, for example using liver, skin, testis, and colon cells, has been developed and validated successfully. The validation studies have been organized as collaborative studies of the Mammalian Mutagenicity Study Group belonging to the Japanese Environmental Mutagen Society and have been published. The other recent development of the micronucleus test is automated evaluation systems. Image analysis and flow cytometry were introduced to the test system with great success. These automated methods are being validated for regulatory purposes. The in vivo multiple end point assay system, which is more efficient, is also discussed here. When we use transgenic mutagenicity model animals in the micronucleus assay, we can obtain information on both gene mutation and chromosomal aberrations concomitantly, and possibly on DNA damage when the micronucleus assay is combined with the comet assay. Such a multiple end point genotoxicity assay system should be highly appreciated from the viewpoint of animal welfare.

The cytokinesis-block micronucleus (CBMN) assay was originally developed as an ideal system for measuring micronuclei; however, it can also be used to measure nucleoplasmic bridges (NPBs), nuclear buds, cell death (necrosis or apoptosis) and nuclear division rate. Current evidence suggests that (1) NPBs originate from dicentric chromosomes in which the centromeres have been pulled to the opposite poles of the cell at anaphase and are therefore indicative of DNA misrepair, chromosome rearrangement or telomere end-fusions, (2) NPBs may break to form micronuclei, (3) the nuclear budding process is the mechanism by which cells remove amplified and/or excess DNA and is therefore a marker of gene amplification and/or altered gene dose, (4) cell cycle checkpoint defects result in micronucleus formation, and (5) hypomethylation of DNA, induced nutritionally or by inhibition of DNA methyltransferase can lead to micronucleus formation either via chromosome loss or via chromosome breakage. The strong correlation between micronucleus formation, nuclear budding and NPBs (r = 0.75–0.77, P