Aug 2026· Frontiers in Oncology· Vol 16· 0 citations· 180 references
Medicine
TL;DR
This review gives a comprehensive overview of the function of metals in causing cancer, focusing on pathways such as genotoxicity, mutagenesis, epigenetic modification, and cancer-related signaling.
Abstract
People around the globe are affected by extensive environmental and occupational exposure to heavy metals, which poses a significant threat to various health hazards, with cancer being a major concern. These toxic metals are ubiquitously found in food, air, water, and industrial, agricultural, or pharmaceutical applications. Being non-biodegradable, they accumulate in the living organism. The prolong exposure to these metals can result into hazardous effects in the many organs including respiratory problems, gastrointestinal disorders, renal issues, and skin lesions etc. Arsenic (As), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Mercury (Hg), and Lead (Pb) are the most common heavy metals causing carcinogenicity through both genetic and epigenetic mechanisms. The literature indicates that DNA damage, deregulation of gene expression, interference with cell signaling, etc., contribute to metal-induced carcinogenesis. Changes in epigenetic processes, such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs, can disturb normal cell function and may even lead to cancer. However, the molecular mechanism remains poorly understood. Advancements in the field have underscored the critical roles of genetic mutations and epigenetic modifications in metal-induced tumor formation. This review gives a comprehensive overview of the function of metals in causing cancer, focusing on pathways such as genotoxicity, mutagenesis, epigenetic modification, and cancer-related signaling. Furthermore, with the ultimate goal of reducing the burden of this disease, the targeted preventive strategies, such as reducing the emission of these toxic metals into the environment from mining to industries, or other sources, and the need for social interventions, have been discussed.
Heavy metals and metalloids, including arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), and mercury (Hg), are well-recognised human carcinogens, and the molecular mechanisms underlying their carcinogenicity are incompletely characterised. In this review, we critically discuss and synthesise the available evidence on how heavy metals and metalloids contribute to cancer development by inducing ROS, oxidative stress, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, and alterations in apoptotic regulators such as p53, Bax, and Bcl-2. Metal-specific differences in genotoxic versus cytotoxic mechanisms and assessing endogenous protective responses, including metallothionein sequestration, antioxidant pathways, and chelation, are included. An extended analysis of the toxicodynamics of metal mixtures is also made, focusing on a realistic but underexplored exposure scenario. Co-occurring metal combinations, such as As-Cd-Cr-Pb, produce endpoint-specific interaction profiles that pose a greater risk for neurological and genotoxic effects than for renal endpoints and cardiovascular effects, depending on the binary combination. Cd and As co-exposure produces synergistic DNA damage 3–5 times greater than predicted from single-metal effects through concurrent p53 dysfunction and ROS overload. Evaluation of the role of gut microbiome interactions in modulating metal bioavailability and carcinogenic potential, limitations of traditional animal models for mixture risk assessment, and emerging technologies, including single-cell sequencing, CRISPR-based functional genomics, and organ-on-chip platforms that may resolve current knowledge gaps, are included.
Sneha Dhanasekaran, K. Dhaneesh· Toxicology and industrial he...· 0 citations
Cadmium chloride (CdCl) is a highly dangerous heavy metal commonly used in electroplating, pigment production, battery manufacturing, plastic stabilization, and other laboratory settings. Due to the speed of industrial growth and human activities, cadmium levels in air, water, and soil have gone up dramatically, This way the compound is a leading reason for environmental and occupational contamination of health. Essential trace elements are those the body relies on but with cadmium, the body does not. In fact, its biological half-life is up to forty years, making the chemical progressively accumulate in tissues. Although the kidney has long been known as the prime organ involved in chronic lead poisoning, cadmium absorption actually causes rapid damage to the liver due to this organ's primary role in metabolism and detoxification of foreign substances (xenobiotics). CdCl liver accumulation initiates many pathological responses including overproduction of reactive oxygen species (ROS), exhaustion of the cell's antioxidant systems, mitochondrial malfunctions, release of inflammatory cytokines, cell death, and fibrosis. At a larger level of tissues and functions, all these changes cause disturbances in liver structure and function leading to hepatocellular injury. Oxidative stress and disruption of calcium homeostasis are just two mechanisms of cadmium toxicity besides other effects like antioxidant enzyme inhibition, DNA and membrane (lipid) damage, and activation of several intracellular signaling pathways such as NF-B, MAPK, and Nrf2. From a histological standpoint, changes include liver cell (hepatocyte) alterations, widened blood sinuses, cells of the immune system coming into the tissue, blood vessels in a state of congestion, spots of necrosis (cell death), and fibrosis. From a clinical point of view, liver damage caused by CdCl is seen as an increase in the levels of some biomarkers, viz. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin, as indicators of disease state changes and alteration of enzyme activities for antioxidant defense (e.g. glutathione peroxidase).The article reviews the present state of knowledge on cadmium environmental exposure sources, toxicokinetic pattern of CdCl, mechanisms responsible for cadmium-induced liver damage, and the corresponding histopathological and biochemical manifestations. Comprehending the molecular events involved is a crucial step toward the designing of strategies aimed at preventing cadmium-induced liver injuries identification of biological indicators of exposure, and formulation of new ways of treatment that will lessen liver damage caused by cadmium exposure.
Amit Kumar Patra, Yeduru Krishna Reddy· International Journal of Lat...· 0 citations
The heavy metal contamination of water, food, and soil is a widely recognized global problem. Yet the strategies commonly used to evaluate the impact of heavy metal contamination on human health typically do not account for the metabolic pathways of metals in living cells. Exposure metrics like Estimated Daily Intake, Hazard Quotient, Hazard Index, and Cancer Risk are simple and inexpensive, and easy to compare to regulatory limits, but they do not provide much information about underlying biological mechanisms: they assume metals are absorbed at a constant rate, do not consider the effects of metal mixtures, and disregard the non-linear cellular damage increasingly shown in in vitro genotoxicity studies. In vitro assays, however, directly demonstrate damage to DNA and chromosomes, and consistently implicate oxidative stress as a common mechanism through which cadmium, arsenic and chromium act; and these assays are seldom connected to actual dietary or drinking water exposures. This review combines the two methods, using contamination data from high-risk environments and data from occupational and environmental biomonitoring studies, which already demonstrate a measurable relationship between exposure and cellular damage. This type of integration is now feasible using newer tools such as physiologically based pharmacokinetic modeling, adverse outcome pathways, and omics-based biomarkers. Building on these, the review proposes a concentration-response approach for assessing heavy metal risk in food. This approach moves beyond a purely statistical exercise and offers a biologically grounded model with real-world implications for the setting and harmonization of international food safety standards. It is based on bioaccessibility-corrected exposure estimates and in vitro-to-in vivo extrapolation.
Manisha Jain, S. Sachdeva, G. Bharat· Genetics and Molecular Resea...· 0 citations
This critical narrative review integrates evidence on major environmental genotoxin classes, exposure routes, molecular mechanisms, human biomonitoring, disease associations and risk-assessment practice for well-established and less mature evidence domains.
Omoighele F. Akhigbe, O. Abutu, N. Y. Wike et al.· Asian Journal of Research in...· 0 citations
Although exposure to heavy metals such as cadmium and inorganic arsenic has declined in recent decades, they remain prevalent environmental contaminants in food, drinking water, and tobacco smoke. This study aimed to identify and compare molecular endpoints of arsenite and cadmium toxicity at the gene and protein expression levels, with a focus on metal homeostasis, the oxidative stress response and redox-regulated processes. Human bronchial epithelial cells (BEAS-2B) were used as an in vitro model. First, the appropriate exposure conditions were defined by assessing cytotoxicity and intracellular metal accumulation. The cells were then incubated with 1–10 µM NaAsO2 or 1–5 µM CdCl2 for 24 h, after which gene and protein expression were analyzed. When compared to arsenite, cadmium was a markedly stronger inducer of metallothionein (MT) expression, indicating distinct effects on metal homeostasis. Both metals induced a concentration-dependent upregulation of oxidative stress-related genes. Cadmium led to a stronger activation of NF-κB signaling, while arsenite decreased selenoprotein-associated gene expression and affected genes involved ferroptosis regulation. Differences in gene and protein expression patterns were also observed, suggesting that transcriptional responses do not necessarily translate into corresponding changes at the protein level after 24 h. These findings highlight shared and compound-specific mechanisms, as well as the importance of multi-level analyses.
Martin Link, Jana Kuhn, M. Parsdorfer et al.· International Journal of Mol...· 0 citations
Chronic exposure to heavy metals and occupational hazards is positively associated with carcinogenesis, although the underlying mechanisms remain poorly understood. The present study evaluated the association between heavy metal exposure and epigenetic alterations/modifications in blood, urine, and tissue samples from patients with UBC and control. ICP-MS measured heavy metal concentrations in blood, urine, and tissue samples, whereas ELISA assessed epigenetic modifications. The study categorically revealed that patients with UBC exhibited significantly elevated blood lead levels and urinary cadmium, arsenic, and chromium compared with controls. Exposure to heavy metals has been associated with changes in gene expression in urothelial bladder cancer (UBC), suggesting that environmental carcinogens may play a vital role in development and progression of bladder tumour.
Ganesh Kumar Verma, Deepika Saini, P. Chaudhary et al.· Gene· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
