Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans ...only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line. The sensitivity of twelve hepatic cell lines was investigated in single cell gel electrophoresis assays. Furthermore, characteristics of these lines were studied which are relevant for their use in genotoxicity assays (mitotic activity, p53 status, chromosome number, and stability). Three lines (HuH6, HCC1.2, and HepG2) detected representatives of five classes of promutagens, namely, IQ and PhIP (HAAs), B(a)P (PAH), NDMA (nitrosamine), and AFB
1
(aflatoxin), and were sensitive towards reactive oxygen species (ROS). In contrast, the commercially available line HepaRG, postulated to be a surrogate for hepatocytes and an ideal tool for mutagenicity tests, did not detect IQ and was relatively insensitive towards ROS. All other lines failed to detect two or more compounds. HCC1.2 cells have a high and unstable chromosome number and mutated p53, these features distract from its use in routine screening. HepG2 was frequently employed in earlier studies, but pronounced inter-laboratory variations were observed. HuH6 was never used in genotoxicity experiments and is highly promising, it has a stable karyotype and we demonstrated that the results of genotoxicity experiments are reproducible.
Scope
Obesity causes DNA damage, which is causally related to several disorders including cancer, infertility, and cognitive dysfunctions. The aim of this study is to investigate whether weight loss ...improves the integrity of the genetic material.
Methods and Results
Overweight mice are fed ad libitum either with a Western diet (WD), with a 40% caloric restricted WD, or with a high carbohydrate low protein (HCLP) diet. Caloric restriction and also the HCLP diet lead to ca. 30% weight loss, which is paralleled by decreased DNA damage (“comet” formation) and oxidative damage of purines in inner organs, additionally the activity of nucleotide excision repair increased. The effects are more pronounced in animals that have received the HCLP chow. Results of biochemical analyses indicate that the reduction of DNA damage is associated with a decrease of pro‐inflammatory cytokines and lower insulin levels.
Conclusion
The study indicates that weight loss may prevent obesity‐associated adverse health effects due to reduction of overall DNA damage.
Weight loss of overweight mice via reduced consumption of a high‐fat Western diet or by a high‐carbohydrate diet leads to reduced DNA damage, decreased formation of oxidized purines in several inner organs, and additionally causes an increase of the activity of nucleotide excision repair. These processes may be causally related to a decline of the levels of pro‐inflammatory cytokines and reduction of the insulin concentrations in the blood, which are observed after the weight loss.
Results of a number of studies indicate that electroplaters have increased cancer risks as a consequence of exposure to genotoxic metals such as chromium (VI) and nickel. These effects may be due to ...induction of damage of the genetic material which plays a key role in the etiology of cancer, and it was found that workers in galvanization factories exhibited increased levels of DNA damage. The aim of the present study was to investigate genetic stability in workers of a bright plating factory who are exposed to chromium (Cr) and cobalt (Co). Exfoliated cells were collected from the buccal and nasal mucosa of workers (n = 42) and matched controls (n = 43) and analyzed for induction of micronuclei (MN) which are formed as a consequence of chromosomal aberrations. In addition, other nuclear anomalies namely nuclear buds (Nbuds) which are formed as a consequence of gene amplification and markers indicating different stages of cell death (condensed chromatin, karyorrhexis, karyolysis, and pyknosis) were also assessed. No evidence was noted for induction of MN, but significantly increased rates of Nbuds in cells from both, buccal and nasal mucosa, were found. Parameters which are indicative for cytotoxic effects were more pronounced in nasal cells and rose with duration of employment period. Overall, our findings indicated that no apparent chromosomal damage occurred in bright electroplaters. However, data demonstrated that acute cytotoxic effects may lead to inflammations and/or lesions in epithelia of the respiratory tract of the workers.
Abstract
Background
Schools are key settings for delivering mental illness prevention in adolescents. Data on stakeholders’ attitudes and factors relevant for the implementation of Internet-based ...prevention programmes are scarce.
Methods
Stakeholders in the school setting from Austria and Spain were consulted. Potential facilitators (e.g. teachers and school psychologists) completed an online questionnaire (N=50), policy makers (e.g. representatives of the ministry of education and health professional associations) participated in semi-structured interviews (N=9) and pupils (N=29, 14–19 years) participated in focus groups. Thematic analysis was used to identify experiences with, attitudes and needs towards Internet-based prevention programmes, underserved groups, as well as barriers and facilitators for reach, adoption, implementation and maintenance.
Results
Experiences with Internet-based prevention programmes were low across all stakeholder groups. Better reach of the target groups was seen as main advantage whereas lack of personal contact, privacy concerns, risk for misuse and potential stigmatization when implemented during school hours were regarded as disadvantages. Relevant needs towards Internet-based programmes involved attributes of the development process, general requirements for safety and performance, presentation of content, media/tools and contact options of online programmes. Positive attitudes of school staff, low effort for schools and compatibility to schools’ curriculum were seen as key factors for successful adoption and implementation. A sound implementation of the programme in the school routine and continued improvement could facilitate maintenance of online prevention initiatives in schools.
Conclusions
Attitudes towards Internet-based mental illness prevention programmes in school settings are positive across all stakeholder groups. However, especially safety concerns have to be considered.
Background
Online preventive interventions can help to reduce the incidence of mental disorders. Whereas knowledge on stakeholders’ attitudes and factors relevant for successfully integrating online ...treatment into existing healthcare systems is available, knowledge is scarce for online prevention.
Methods
Stakeholders from Germany, Switzerland, Austria and Spain were surveyed. Potential facilitators/delivery staff (e.g. psychologists, psychotherapists) completed an online questionnaire (n = 183), policy makers (i.e. from the governing sector or health insurance providers) participated in semi-structured interviews (n = 16) and target groups/potential users of mental illness prevention (n = 49) participated in ten focus groups. Thematic analysis was used to identify their experiences with and attitudes and needs regarding online programmes to prevent mental disorders. Additionally, it was examined which groups they consider underserved and which factors they consider as fostering and hindering for reach, adoption, implementation and maintenance (cf. RE-AIM model) when integrating online prevention into existing healthcare systems.
Results
Main advantages of online mental illness prevention are perceived in low structural and psychological barriers. Lack of personal contact, security, privacy and trust concerns were discussed as disadvantages. Relevant needs are high usability and target group appropriateness, evidence for effectiveness and the use of motivational tools.
Conclusions
Positive attitudes among stakeholders are the key for successful integration of online mental illness prevention into existing healthcare systems. Potential facilitators/delivery staff must receive training and support to implement these programmes; the programmes must be attractive and continuously evaluated, updated and promoted to ensure ongoing reach; and existing infrastructure and contextual factors must be considered.
Background
Students beginning university are at a heightened risk for developing mental health disorders. Online prevention and early intervention programmes targeting mental health have the ...potential to reduce this risk, however, previous research has shown uptake to be rather poor. Understanding university stakeholders’ (e.g. governing level and delivery staff DS and students) views and attitudes towards such online prevention programmes could help with their development, implementation and dissemination within university settings.
Methods
Semi-structured interviews, focus groups and online surveys were completed with staff at a governing level, university students and DS (i.e. student health or teaching staff) from six European countries. They were asked about their experiences with, and needs and attitudes towards, online prevention programmes, as well as the factors that influence the translation of these programmes into real-world settings. Results were analyzed using thematic analysis.
Results
Participating stakeholders knew little about online prevention programmes for university settings; however, they viewed them as acceptable. The main themes to emerge were the basic conditions and content of the programmes, the awareness and engagement, the resources needed, the usability and the responsibility and ongoing efforts to increase reach.
Conclusions
Overall, although these stakeholders had little knowledge about online prevention programmes, they were open to the idea of introducing them. They could see the potential benefits that these programmes might bring to a university setting as a whole and the individual students and staff members.