Abstract Humans are continually exposed to a diverse array of environmental chemicals that can damage DNA and compromise genomic integrity. Among these genotoxic agents, acetaldehyde, acrolein, aristolochic acids, and vinyl chloride are particularly concerning due to their widespread presence in industrial emissions, dietary sources, and lifestyle-related exposures such as smoking and alcohol consumption. These compounds can induce structurally distinct forms of DNA damage including bulky DNA adducts, interstrand crosslinks, and other replication-blocking lesions. While canonical DNA repair pathways serve as the primary defense against such DNA damage, some lesions persist, challenging the capacity of DNA repair systems. If not efficiently repaired, DNA lesions may disrupt replication and transcription. In many cases, translesion synthesis polymerases are recruited to bypass unrepaired lesions, introducing mutations that contribute to agent-specific mutational signatures found in cancer genomes. This review systematically examines how each of these four exogenous chemicals induces DNA damage, the DNA repair pathways responsible for removing their lesions, and the role of translesion synthesis in shaping their mutational signatures. We also highlight how three-dimensional genome organization regulates lesion susceptibility and repair, contributing to variability of mutational landscapes.

Lead pollution from metalliferous mines can have major environmental and health effects long after the mines have closed. Animals living near derelict mine sites can inadvertently ingest lead-contaminated soils, causing them to accumulate lead and potentially experience significant adverse health effects. Human food products, such as eggs, produced near metalliferous mines may also be contaminated with lead. The focus of this case study was to determine whether free-range chickens living near a derelict lead mine had high lead body burdens, whether they were producing eggs with elevated lead concentrations, and whether these eggs could be hazardous to human health. Soil samples and chicken egg, feather, blood, and bone samples were collected from a small farm near an abandoned metalliferous mine. The soil in and around the chicken pens contained lead concentrations that were elevated above established soil lead baseline concentrations. The lead concentrations in the chicken feather, blood, and bone samples were consistent with lead toxicity and indicated long-term, continuous exposure. Finally, the lead concentrations in the eggs were significantly greater than those found in commercial eggs. Based on previously established lead benchmark dose levels, humans, and in particular, children, could experience adverse health impacts if they routinely consumed these eggs. Environmental lead contamination continues to pose a major health risk for humans, and further research, understanding, and awareness are required to safeguard the public from the risks of consuming food produced near derelict mines

The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through in vitro tests, followed by in vivo experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate in vitro testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are in vitro three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of in vitro 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.

Nurses and midwives are integral to public health promotion; in the UK, they are advised to act as role models by their governing body, but overweight or obesity rates are high. We explored whether obesity and dietary habits are related to attitudes towards healthy role modelling and health promotion practice. A total of 346 pre-registered UK nurses and midwives (92.6% female; 18–53 years) completed an online survey. Items included body composition, dietary habits assessed by the Lifestyle Behaviour Questionnaire (LBQ), attitudes towards being role models for health (RA: role attitudes) and attitudes toward health promotion practice (ATHPP): 33.8% of the sample self-reported as overweight or obese; 67.6% did not consume 5-a-day portions of fruit/veg; 31.5% reported a healthy diet; and 89.6% believed their diet could be healthier. Positive RA was significantly linked to health promotion engagement (HP) (ß = 0.33, p < 0.001). Positive ATHPP was significantly predicted by lower BMI (ß = −0.08, p = 0.078), positive RA (ß = 0.67, p < 0.001), lower HP (ß = −0.25, p < 0.001) and male gender (ß = 0.09, p = 0.02). Greater confidence in patients valuing healthcare professional’s advice was predicted by healthier diet (ß = 0.11, p = 0.03), lower BMI (ß = −0. 16, p < 0.01), more positive RA (ß = 0.14, p < 0.01) as well as HP engagement during training (ß = 0.20, p < 0.01). One’s own motivation to promote health, similarly to ATHPP, was predicted by RA (ß = 0.17, p = 0.001) and previous HP engagement (ß = 0.39, p < 0.001). Findings show that overweight and obesity are prevalent in pre-registered nurses and midwives; the majority did not consume a healthy diet. Individual’s body composition, diet and attitudes towards role modelling are positively associated with their attitudes towards, and confidence in, health promotion practice. Experiences of health promotion practice during training can have either a positive or a negative influence on attitudes. Mentors and educators could actively promote healthy lifestyles for pre-registered nurses and midwives and facilitate more opportunities for health promotion practice during placements, which includes time for reflection

This study aims to investigate the potential risk of As contamination in rice cultivated in agricultural fields affected by mica mining in Jharkhand, India. For this purpose, soil and rice grain samples were collected from the agricultural fields 500 m (Zone 1) and 50 m (Zone 2) from the mica mines. Total As (mean ± SD) content in the Zone 1 and Zone 2 were 4.79 ± 0.11 and 44.74 ± 1.01 mg kg−1, respectively. The available As was of 3.76 ± 0.22 mg kg−1 in Zone 1 and 1.55 ± 0.02 mg kg−1 in Zone 2. The As in rice grain varied from 1.09 ± 0.08 mg kg−1 in Zone 2 to 0.11 ± 0.02 in Zone 1. From sequential extraction the concentration of As in Zone 2 followed the order: amorphous (14.59 mg kg−1) > crystalline iron oxide-bound phases (6.27 mg kg−1) > exchangeable fraction (0.62 mg kg−1) > water-soluble (0.15 mg kg−1). Amorphous iron oxide bound As have significant (p < 0.05) positive correlation with As in rice plant parts. From self-organizing map and positive matrix factorization analysis, mining activities and improper disposal of mica mining waste were recognized as significant contributors to As toxicity in the region. The measured total cancer risk for children, men and women were 3.10 × 10–2, 7.7 × 10–3 and 8.4 × 10–3, respectively, exceeding the tolerable limit of 10–5. The hazard index values were below toxic thresholds, children experienced the highest impact, followed by women and men

The current study aimed to investigate genomic instabilities in healthcare workers who may experience varying levels of radiation exposure through various radiological procedures. It also sought to determine if factors related to the work environment and dosimeter reading could effectively explain the observed genomic instabilities. Utilizing the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes, we assessed a spectrum of genomic aberrations, including nucleoplasmic bridge (NPB), nuclear budding (NBUD), micronucleus (MN) formation, and total DNA damage (TDD). The study uncovered a statistically significant increase in the occurrence of distinct DNA anomalies among radiology workers (with a significance level of P < 0.0001 for all measurements). Notably, parameters such as total working hours, average work duration, and time spent in projection radiography exhibited significant correlations with MN and TDD levels in these workers. The dosimeter readings demonstrated a positive correlation with the frequency of NPB and NBUD, indicating a substantial association between radiation exposure and these two genomic anomalies. Our multivariable models identified the time spent in projection radiography as a promising parameter for explaining the overall genomic instability observed in these professionals. Thus, while dosimeters alone may not fully explain elevated total DNA damage, intrinsic work environment factors hold potential in indicating exposure levels for these individuals, providing a complementary approach to monitoring.

The COVID-19 vaccine is being rolled out globally. High and ongoing public uptake of the vaccine relies on health and social care professionals having the knowledge and confidence to actively and effectively advocate it. An internationally relevant, interactive multimedia training resource called COVID-19 Vaccine Education (CoVE) was developed using ASPIRE methodology. This rigorous six-step process included: (1) establishing the aims, (2) storyboarding and co-design, (3) populating and producing, (4) implementation, (5) release, and (6) mixed-methods evaluation aligned with the New World Kirkpatrick Model. Two synchronous consultations with members of the target audience identified the support need and established the key aim (Step 1: 2 groups: n = 48). Asynchronous storyboarding was used to co-construct the content, ordering, presentation, and interactive elements (Step 2: n = 14). Iterative two-stage peer review was undertaken of content and technical presentation (Step 3: n = 23). The final resource was released in June 2021 (Step 4: >3653 views). Evaluation with health and social care professionals from 26 countries (survey, n = 162; qualitative interviews, n = 15) established that CoVE has high satisfaction, usability, and relevance to the target audience. Engagement with CoVE increased participants’ knowledge and confidence relating to vaccine promotion and facilitated vaccine-promoting behaviours and vaccine uptake. The CoVE digital training package is open access and provides a valuable mechanism for supporting health and care professionals in promoting COVID-19 vaccination uptake

In utero development represents a sensitive window for the induction of mutations. These mutations may subsequently expand clonally to populate entire organs or anatomical structures. Although not all adverse mutations will affect tissue structure or function, there is growing evidence that clonally expanded genetic mosaics contribute to various monogenic and complex diseases, including cancer. We posit that genetic mosaicism is an underestimated potential health problem that is not fully addressed in the current regulatory genotoxicity testing paradigm. Genotoxicity testing focuses exclusively on adult exposures and thus may not capture the complexity of genetic mosaicisms that contribute to human disease. Numerous studies have shown that conversion of genetic damage into mutations during early developmental exposures can result in much higher mutation burdens than equivalent exposures in adults in certain tissues. Therefore, we assert that analysis of genetic effects caused by in utero exposures should be considered in the current regulatory testing paradigm, which is possible by harmonization with current reproductive/developmental toxicology testing strategies. This is particularly important given the recent proposed paradigm change from simple hazard identification to quantitative mutagenicity assessment. Recent developments in sequencing technologies offer practical tools to detect mutations in any tissue or species. In addition to mutation frequency and spectrum, these technologies offer the opportunity to characterize the extent of genetic mosaicism following exposure to mutagens. Such integration of new methods with existing toxicology guideline studies offers the genetic toxicology community a way to modernize their testing paradigm and to improve risk assessment for vulnerable populations. Environ. Mol. Mutagen. 61:55–65, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Cancer is a common name for about 200 diseases characterized by abnormal cell growth. According to Kundson (1), the causes of cancer may be classified into the following groups: 1. genetic predisposition 2. environmental factors 3. environmental factors superimposed on genetic predisposition 4. unknown factors Typical examples of the first group are childhood cancers such as retinoblastoma (a genetically predisposed malignancy of the retina), neuroblastoma (a malignancy of the brain), and Wilms’ tumor (a malignancy of the kidney). In adults, an example is polyposis of the colon, a genetic condition that frequently leads to colon cancer. The third group is represented by xeroderma pigmentosum, a genetic condition characterized by a deficient DNA excision repair mechanism (see the discussion later in this chapter). Individuals so predisposed develop skin cancer when exposed to ultraviolet light. The variable susceptibility of the population to the carcinogenic effects of cigarette smoke may also reflect genetic predisposition. Very little can be said about the fourth group because the causes of this group of cancers are not known. Groups 2 and 3 combined (i.e., cancer attributable to environmental causes, with or without genetic predisposition) probably account for 60– 90% of all cancers (2). The environment, in this context, involves not only air, water, and soil, but also food, drink, living habits, occupational exposure, drugs, and practically all aspects of human interaction with the surroundings. This definition implies that a great majority of cancers could be prevented by avoiding exposure to potential carcinogens and by changing living habits. It is therefore not surprising that the study of chemical carcinogenesis represents a major aspect of environmental toxicology. Table 5.1 gives an overview of estimated environmentally associated cancer mortality or incidence in the United States. The data presented in this table have to be considered as rough estimates only. There are great variations in the estimates, depending on the investigators and their methods of collecting the pertinent statistics. The Office of Technology Assessment report on cancer risk offers a more in-depth treatment of this subject.

Cigarette smoking leads to various detrimental health outcomes. Tobacco companies produce different brands of cigarettes that are marketed as reduced harm tobacco products. Early examples included “light” cigarettes, which differ from regular cigarettes due to filter ventilation and/or differences in chemical constituents. In order to establish baseline similarities and differences among different tobacco brands available in Canada, the present study examined the cytotoxicity, mutagenicity, clastogenicity, and gene expression profiles of cigarette smoke condensate (CSC) from three tobacco products, encompassing a full‐flavor, blonde, and “light” variety. Using the Salmonella mutagenicity assay, we confirmed that the three CSCs are mutagenic, and that the potency is related to the presence of aromatic amines. Using the Muta™Mouse FE1 cell line we determined that the CSCs were clastogenic and cytotoxic, but nonmutagenic, and the results showed few differences in potencies among the three brands. There were no clear brand‐specific changes in gene expression; each brand yielded highly similar expression profiles within a time point and concentration. The molecular pathways and biological functions affected by exposure included xenobiotic metabolism, oxidative stress, DNA damage response, cell cycle arrest and apoptosis, as well as inflammation. Thus, there was no appreciable difference in toxicity or gene expression profiles between regular brands and products marketed as “light,” and hence no evidence of reduced harm. The work establishes baseline CSC cytotoxicity, mutagenicity, and expression profiles that can be used as a point of reference for comparison with data generated for products marketed as reduced harm and/or modified risk tobacco products. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.