Mutagenic factors in the environment impacting human and animal health (2025)

In our day-to-day life, mutagenic factors especially dominate in the environment and are considered responsible for causing and/or aggravating a number of diseases. Japanese Environmental Mutagen Society reported that the environmental mutagens are mostly available in the environment as chemical and physical agents and causing human health hazard (JEMS 2017). The environmental mutagens are associated with multiple diseases, and which may transform into carcinogenesis in humans (Goyal et al. 2021).

Global industrialization together with the development of modern healthcare systems has led to an exponential growth in the number of toxics we use for various purposes. The networking of mutagenic factors is mostly involved in induction of oxidative stress through a variety of sources including radiations (ionizing and non-ionizing) including from radiotherapy, chemicals, toxic metals, fine particles, lifestyle & social factors, medications or use of drugs, environmental factors (such as, climate change, pollutions) and other risk factors of food chain. Several natural or manmade toxicants are also responsible for the metabolic as well as neurological diseases and male infertility, for example the recent findings of coronavirus (COVID-19)-induced neuronal dysfunctions, and impairment of fertility, apart from other health issues. Including these, thousands of environmental contaminants penetrate daily into our environment and exert various kinds of stress response on human health.

This special issue contains 15 articles reporting a role of mutagenic factors in the environment and that impacting human health. In general, the mutagenic factors which are associated with the human and animal health, disseminating the physical, chemical and biological contamination factors.

Article, “Molecular docking and dynamics studies of cigarette smoke carcinogens interacting with acetylcholinesterase and butyrylcholinesterase enzymes of the central nervous system” (Jamal and Alharbi 2021) discusses the cigarette smoking induced free radical formation found as carcinogen and lead to cause neuronal dysfunctions. Computational studies showed the interaction between cigarette smoking carcinogens and central nervous system (CNS) targeting enzymes acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Study concludes that the cigarette smoking may cause serious damage to CNS.

Article, “A systematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones” (Mohammadi et al. 2021) provides a very important systematic review on glyphosate herbicide, which has been recognized as a contaminant in water, agricultural crops and food products. The study explores a potential role of glyphosate herbicide in balancing of sexual hormones and their effects on reproductive system. It concludes that this herbicide may lead to cause hormonal dysfunctions.

Article, “Mechanical dependency of the SARS-CoV-2 virus and the renin-angiotensin-aldosterone (RAAS) axis: a possible new threat” (Sen et al. 2021) reviewed the existing pathogen SARS-CoV-2 which has been detected as highly effective viral threat of 21^st century. Authors pointed out the mechanism how virus enters the cells and cause body´s physiological balance. The correlation of entering virus into cells through the RAAS axis is of interest mainly how SARS-CoV-2 modulates the RAAS axis and leads to cause several health issues. The study also focuses on the possibilities of drug development and designing by targeting the modulation of the RAAS axis against SARS-CoV-2.

Article, “Unboxing the molecular modalities of mutagens in cancer” (Kumari et al. 2021) discusses the association of environmental mutagenic factors with human cancer. The study reveals the interplay between DNA damage response and immune system mechanisms due to myriad of environmental causing factors such as physical, chemical, and biological. Additionally, the DNA damage and repair mechanisms have been discussed to broaden the understanding of mutagenicity and carcinogenicity of human cancers. Moreover, DNA repair targeted therapies and chemotherapeutic agents have been discussed along with several future possibilities with antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents.

Article, “Free radical biology in neurological manifestations: mechanisms to therapeutics interventions” (Tripathi et al. 2021) provides a better understanding of free radicals and redox signaling. Oxidative stress induced free radical formation may enhance the reactive oxygen species (ROS) in the cellular system which may lead to cause severe inflammatory diseases, metabolic disorders, and neurological defects. The study reveals that any increase in ROS may lead to cause cell death involving different signaling pathways. It discusses the role of oxidative stress in synaptic plasticity and axonal regeneration through the modulation of various signaling molecules along with potential therapeutic approaches. The factors associated with such damages are mainly chemical i.e., drug overdosing, toxic heavy metals, smoking, alcohol; biological i.e. pesticides, viruses, bacterial contaminations and physical i.e. ionizing radiation and ultraviolet radiation. The study concludes that due to these mutagenic factors it may lead to cause pathogenesis and progression of neurodegenerative diseases and defects.

After consulting many review papers, a research article “Impact of ginseng on neurotoxicity induced by cisplatin in rats”, written by Hussein and Yousef 2021 showed promising data on the neuroprotectant ginseng against neurological damages and diseases. The study reported that cisplatin chemotherapy for neuronal disturbance may trigger memory impairment and cognitive disability and therefore, this study explores the neuroprotective impact of ginseng extract for the treatment of neurological and behavioral abnormalities. The study includes animal experiments by grouping animals into several treatment mechanisms based on doses and days. Authors obtained several parameters i.e., behavioral study, antioxidants, neurotransmitters and neuroinflammatory molecules were investigated along with apoptotic and dementia markers. The article concludes that ginseng as a neuroprotectant was capable to counteract the memory dysfunction which was induced by cisplatin via reducing oxidative stress. The study shows better possibilities to use ginseng as a neuroprotectant for future studies.

Article, “The mutagenic effect of tobacco smoke on male fertility” (Omolaoye et al. 2021) discusses the possible association between tobacco smoke and their harmful effects on male fertility factors. This is a very interesting study especially for the population who are consuming nicotine and its metabolites. It has been well reported that several mutagenic factors i.e., radiation, radiotherapy, chemical contamination, obesity, lifestyle factors may induce oxidative stress and lead to cause sperm and testicular damages (Kesari et al. 2018; Roychoudhury et al. 2022). Although, this study reports that cigarette smoking has shown higher chances to cause not only a decrease in sperm parameters for example, sperm count, motility, and an increase in abnormal sperm morphology, but also genetic and epigenetic aberrations in spermatozoa. This study reviews both animal and human models, where it has been focused to explore the genetic level of damages i.e., genomic instability. The study provides clear evidence of smoking that has a mutagenic effect on sperm and also its role in male infertility.

Article, “Epigenetics; a new warrior against cardiovascular calcification, a forerunner in modern lifestyle diseases” (Dutta et al. 2021a) discusses about the lifestyle factors which may affect our health. This review summarizes the reason behind the generation of arterial and aortic valve calcification. It may also explore related signaling pathways and the detrimental effects of calcification. This study reports an implementation of epigenetics as a novel approach to protect the harmful effects of calcification.

Article, “Unravelling the molecular mechanism of mutagenic factors impacting human health” (Goyal et al. 2021) reveals the molecular mechanism of physical and chemical mutagens. The physical mutagens are classified mostly as radiations i.e. X-rays, radiotherapy, gamma rays, UV rays, however, chemical mutagens mostly listed are polycyclic aromatic hydrocarbons (PAHs), bisphenol A (BPA) and several heavy metals i.e. chromium, lead, mercury, arsenic, cadmium etc. These mutagenic toxicants may lead to cause DNA damage, carcinogenesis with biological process and chromosomal abnormalities. The study highlights that oxidative stress may produce ROS which may lead to multiple disorders and impact human health. An important aspect of this study is that they discussed on possible parameters through which the mutagenic factors may be estimated.

In this series, a research article, “TiO₂-NPs and cadmium co-exposure: in vitro assessment of genetic and genomic DNA damage onDicentrarchus labraxembryonic cells” (Mottola et al. 2021) discusses an individual role of TiO₂-NPs and also with cadmium as co-exposure on Dicentrarchus labrax embryonic cells. TiO₂is most common nanoparticles contamination in the environment and found deleterious effects on human health. This is an interesting study with in vitro model where several important genotoxicity tests were obtained for example, comet assay, diffusion and random amplification of polymorphic DNA (RAPD) to investigate the effects of TiO₂nanoparticles. Majorly, the study investigated an increased level of DNA and apoptotic cells after 48 hrs of TiO₂ exposure, although genotoxic effect of Cd started after 3 hrs of exposure. Most interesting part of this study showed no significant changes in TiO2 with co-exposure with Cd at any exposure time. The study concludes that TiO₂ as an individual exposure may cause DNA strand break and lead to several diseases.

Article, “A perspective review on medicinal plant resources for their anti-mutagenic potentials” (Malik et al. 2021) discusses on the various medicinal plants which may participate as an anti-mutagenic factor. This review provides a better understanding and updates on various mutagenic factors such as physical, chemical, and biological. These toxicants are present mostly in higher amount in the environment and attributes to resultant mutations (and cancer). The study aimed to explore that how medicinal plants come to the rescue and taking an account of medicinal plant resources used as antimutagenic agents. The authors mostly targeted cancer cure and provided therapeutic possibilities with herbal bioactive compounds.

Article, “Environmental and occupational exposure of metals and female reproductive health” (Dutta et al. 2021b) provides a better understating towards metal toxicity for female reproductive health. There are number of environmental and occupational exposures present in our surroundings. In this review several mutagenic factors are listed as they mainlyinclude an exponential growth of human population, uncontrolled rise in industrialization, poorly planned urbanization, and slapdash environment management. Earlier Sengupta et al. (2015) listed out several metals, as reproductive toxins, where it was reported that it may induce hormonal changes including menstrual cycle, ovulation, and fertility. In this continuation, the present review discusses the chronic exposures to the heavy metals that may lead to severe diseases such as endometrial and breast cancers, endometriosis, and menstrual disorders. This review aims to provide possible mechanistic approach to answer the question that how heavy metal affect female reproductive health? This review is an important inclusion in the special issue specially after considering the current scenario of our existing environmental toxicity.

Another article on heavy metals contamination in animal meat and carcinogenesis featured a laboratory-based study. Research article, “Determination of some heavy metals levels in the meat of animal species (sheep, beef, turkey, and ostrich) and carcinogenic health risk assessment in Kurdistan province in the west of Iran” (Raeeszadeh et al.2022), provides several important documentations of metals accumulation in animal meat including sheep, beef, turkeys, and ostriches. The study mainly focuses some highly toxic heavy metals i.e., selenium, lead, cadmium, arsenic, cobalt, zinc, nickel, copper, and chromium which were detected in large group of animals with sample size around 170. This is a very interesting study because higher percentage of population globally are consuming meat or meat products. Metal contaminations are quite obvious in animals particularly in Asian and African countries where pollution levels are very high not only in the environment but also in water at both ground and surface levels. This study reveals that most of heavy metal concentrations were higher to maximum permissible limits specially lead, cadmium, arsenic, zinc, copper, chromium, and nickel. The authors suggest that the contamination level should be decreased or controlled while feeding water or food to the animals in farm houses.

Article, “Mutagens in raw ewe milk in Orava region, northern Slovakia: Metals” (Toman et al. 2022) determined the concentrations of selected mutagenic elements (arsenic, cadmium, cobalt, chromium, copper, iron, manganese, nickel, lead, and selenium) in raw ewe milk from undisturbed environment in Orava – a region in northern Slovakia in eastern Europe where (re) distribution of some of the metals are suspected due to the presence of metallurgical plants in nearby Ostrava region in Czech Republic, and Katowice in Poland. The concentrations of most of the metals in ewe milk were low and under the permissible or recommended limits. However, arsenic and selenium concentrations were elevated and could pose a risk of the mutagenic effect, particularly in children. Further, it was concluded that the relationships between the elements might result in the additive or synergistic effects of metals and increase the risk of their mutagenic effects even in low concentrations.

In continuation to metal toxicity, this is an interesting research article, “Paternal factors in recurrent pregnancy loss: an insight through analysis of non-synonymous single nucleotide polymorphism in human testis specific chaperone HSPA2 gene”, (Mohanty et al. 2021) discusses the role of heat shock protein A2 in spermatogenesis and remodeling of the sperm surface during capacitation. The study reveals that an absence of HSPA2 in mice may lead to infertility, therefore it explores the association between genetic mutation and phenotypic variation in recurrent pregnancy loss (RPL) patients through an in-silico prediction analysis. The experiment was conducted based on computational approach to analyze the functional consequences of the nsSNPs in human HSPA2 gene. The authors concluded that these 18 nsSNPs using a combinatorial bioinformatic approach. Also, itreveals the therapeutic diagnostics and prognostics of HSPA2 for human reproduction.

The theme of this special issue shows great impact towards controlling the environmental deficiencies, which may affect human and animal health. From 15 articles, including both review and research, providing better understanding of networking of mutagenic factors present in the environment, which may not only impact human and animal health but also environment at certain levels. All the guest editors of this special issue would like to extend our vote of thanks to the Editor-in-Chief of the Environmental Science and Pollution Research (Journal) along with entire editorial team. We would also like to thank all the contributing authors for their exceptional and timely contributions. Last but not the least, our sincere appreciation to all the reviewers for their invaluable and critical review comments on manuscripts that were submitted to this special issue.