Search Results (60)

Magnesium (Mg²⁺) has gained oncologists’ attention due to its wide range of biological functions and frequent use as a complementary or integrative agent. This review outlines Mg’s actions, its complex role in carcinogenesis and tumor risk, and clinical issues. Mg²⁺ is essential in numerous biochemical processes, including adenosine triphosphate production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation. Pertinent full-text articles were thoroughly examined, and the most relevant ones were selected for inclusion in this review. There is conflicting scientific evidence about the relationship between Mg²⁺ changes and cancer risk, apart from colorectal cancer. Chronic Mg²⁺ deficiency leads to immune dysfunctions and enhanced baseline inflammation associated with oxidative stress related to various age-associated morbidities and cancer. On the other hand, Mg²⁺ deficiency is associated with drug or chemotherapy-related hypomagnesemia, postoperative pain, cachexia, opioid-induced constipation, normal tissue protection from radiation damage, and prevention of nephrotoxicity. A balanced diet usually provides sufficient Mg²⁺, but supplementation may be necessary in some clinical settings. Full article

Exposure to high-linear energy transfer (LET) heavy ions, such as ²⁸Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of ²⁸Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc^1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc^1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or ²⁸Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, ²⁸Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the ²⁸Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in ²⁸Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to ²⁸Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after ²⁸Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions. Full article

Radon is an inert gas produced by the radioactive decay of uranium-238, commonly found in the environment. Radon and its decay products are the main sources of human exposure to radiation from natural sources. When inhaled, radon’s alpha particles impact lung tissue, potentially causing lung cancer by damaging DNA and altering oxidative processes. This review article addresses the need for a deeper understanding of the genetic and molecular changes associated with radon-induced lung cancer, aiming to clarify key genetic mutations and protein markers linked to carcinogenesis. Particular attention in recent studies has been given to mutations in tumor suppressor genes (RASSF1, TP53), oncogenes (KRAS, EGFR), and changes in the expression levels of protein biomarkers associated with inflammation, stress, and apoptosis. Identifying these markers is critical for developing effective screening methods for radon-induced lung cancer, enabling timely identification of high-risk patients and supporting effective preventive strategies. Summarizing current genetic and protein biomarkers, this review highlights the importance of a comprehensive approach to studying radon-induced carcinogenesis. Understanding these molecular mechanisms could ultimately improve early diagnostic methods and enhance therapy for cancers associated with radon exposure. Full article

The harmful effects of solar radiation on the skin are known and scientifically proven, with recent studies indicating that not only ultraviolet (UV) radiation but also infrared (IR) radiation contributes to skin photoaging and increases the risk of carcinogenesis. Infrared radiation is also responsible for the degradation of protective carotenoids in the skin, the disruption of calcium homeostasis, and the activation of apoptosis pathways. The biological mechanisms underlying these effects include an increased level of reactive oxygen species and increased expression of metalloproteinases in the skin. The aim of this study was to evaluate the photoprotective properties of 10 cold-pressed plant oils in the infrared spectral range from 1000 nm to 2500 nm by assessing their impact on the directional–hemispherical reflectance (DHR) of human skin after their topical application. This study was conducted in vivo on the skin of 12 volunteers, with non-invasive DHR measurements taken before and directly after the application of the oil and 30 min later. Additionally, the correlation between the oil’s compounds (chlorophyll a, chlorophyll b, lycopene, and β-carotene) and antioxidant activity, expressed as the DPPH free radical scavenging capacity, was analyzed in relation to the differences in the skin’s DHR observed. An interesting result was obtained in the context of protecting the skin against IR radiation. A statistically significant increase in the skin’s reflectance after the penetration of the oil (p < 0.05) was observed in the 1700–2500 nm range for the chokeberry, fig, pomegranate, and perilla oils, suggesting their potential as photoprotective agents against IR. These findings indicate that chokeberry, fig, pomegranate, and perilla oils may serve as ingredients in cosmetic formulations designed for broad-spectrum skin photoprotection, complementing traditional UV filters with additional protection against infrared radiation. However, further research is needed to confirm these findings in a larger population. Full article

Childhood radiation is a risk factor for thyroid cancer that became well known after the Chernobyl nuclear plant accident. Although these human cases have been extensively studied, the mechanisms underlying childhood susceptibility to radiation-induced thyroid cancer have yet to be explained. Our previous study showed that neonatal X-irradiation resulted in long-term alterations in the mRNA expression of thyroid cancer-related marker genes, which may be a critical mechanism for understanding the higher radiation sensitivity in young patients. In this study, RNA sequencing (RNA-Seq)-based gene expression analysis was employed to identify thyroid genes whose mRNA expression was changed by neonatal irradiation. Male Wistar rats aged 1 week and 4 months were subjected to cervical X-irradiation at 4 Gy. After 8 weeks, total RNA was extracted from the thyroid and subjected to RNA-Seq analysis to identify differentially expressed genes following irradiation. We identified five upregulated genes (i.e., Adm2, Vnn1, Snph, Gria3, and Cpa4) and one downregulated gene (i.e., Crtac1) explicitly altered by neonatal radiation exposure. Western blotting confirmed the corresponding changes in CPA4 and CRTAC1 expression. The gene expressions identified were also altered in thyroid tumors induced by an iodine-deficient diet. These long-term changes in thyroid gene expression caused by neonatal irradiation may be involved in the increased risk of thyroid carcinogenesis. Full article

Sunlight exposure plays an important role in human health, impacting processes such as mood, blood pressure regulation, and vitamin D₃ production. Solar ultraviolet B radiation initiates vitamin D₃ synthesis in the skin, which is subsequently metabolized into its biologically active form. UVB exposure plays a key role in enabling vitamin D₃ synthesis, but it can also contribute to skin carcinogenesis, creating a complex interplay between its beneficial and harmful effects. Vitamin D deficiency, affecting over half the global population, is linked to a range of chronic diseases, including cancers, cardiovascular conditions, and autoimmune disorders. Simultaneously, excessive solar UVB exposure increases the risk of non-melanoma and melanoma skin cancers through mechanisms involving DNA damage and oxidative stress. This review examines the dual role of UVB radiation in health and disease, focusing on the mechanisms of cutaneous vitamin D₃ synthesis, the epidemiology of skin cancer, and the protective roles of vitamin D₃’s photoproducts and its active metabolite, 1,25-dihydroxyvitamin D₃. Understanding these interconnections is critical for developing strategies that balance adequate sun-induced vitamin D₃ production with skin cancer prevention. Full article

Preoperative or postoperative radiation therapy is broadly employed in patients with rectal carcinoma. Radiotherapy directs high-energy beams of ionizing radiation toward the tumor area to destroy cancer cells. High radiation doses are needed for cell killing. The radiation exposure of the healthy tissues/organs may lead to carcinogenesis. This study describes the evolving role of radiotherapy in rectal cancer management. The present report also reviews epidemiological and dosimetric studies related to the radiation-induced second malignancies from pelvic radiotherapy. Some epidemiological studies have concluded that the second-cancer risk in patients subjected to radiation therapy does not increase compared to unexposed rectal cancer patients. Other researchers found an elevated or a marginally increased probability for second-cancer induction. Dosimetric studies reported cancer risk estimates for critical organs or tissues in the near and far periphery of the treatment volume. Useful information about the effect of the treatment parameters such as the irradiation technique, photon beam energy, and fractionation schedule on the organ-specific second-cancer risk was derived from the dose data analysis. The knowledge of these effects is needed for the selection of the optimal treatment parameters enabling a reduction in the resultant risk of carcinogenesis. Full article

Background/Objective: Ultraviolet (UV) B radiation leads to DNA damage by generating cyclobutane pyrimidine dimers (CPDs). UVB-induced CPDs can also result in immune suppression, which is a major risk factor for non-melanoma skin cancer (NMSC). UVB-induced CPDs are repaired by nucleotide repair mechanisms (NER) mediated by xeroderma pigmentosum complementation group A (XPA). The purpose of this study was to investigate the use of TH as a chemopreventive agent against the development of skin cancer. Method: SKH-1 hairless mice were exposed were fed with TH (0.1% v/v) for two weeks and exposed to a single dose of UVB (180 mJ/cm²). Dorsal skin was harvested 24 h post-UVB exposure for evaluation of DNA damage and repair. Lymph nodes were also harvested to prepare single cell suspension for flow cytometric evaluation. For carcinogenesis experiments, SKH-1 hairless mice were given TH (0.1% v/v) ad libitum and exposed to UVB (180 mJ/cm²) thrice a week for 30 weeks. Results: Feeding SKH-1 hairless mice with TH (0.1% v/v) for two weeks prior to a single dose of UVB (180 mJ/cm²) led to a significant increase in XPA in skin and DNA repair cytokines IL-12 and IL-23 in draining lymph nodes. Furthermore, when subjected to the photocarcinogenesis protocol; mice fed with TH developed significantly fewer tumors in comparison to mice fed on drinking water. Conclusions: Our data demonstrate that TH has a protective effect against UVB-induced DNA damage, immune suppression, and skin cancer. Future studies will further investigate the potential of TH as a preventive treatment for NMSC. Full article

Glioblastoma multiforme (GBM) is a malignant primary brain tumor categorized as a Grade 4 astrocytic glioma by the World Health Organization (WHO). Some of the established risk factors of GBM include inherited genetic syndromes, body mass index, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and therapeutic ionizing radiation. Vascular anomalies, including local and peripheral thrombosis, are common features of GBM. Podoplanin (PDPN), a ligand of the C-type lectin receptor (CLEC-2), promotes platelet activation, aggregation, venous thromboembolism (VTE), lymphatic vessel formation, and tumor metastasis in GBM patients. It is regulated by Prox1 and is expressed in developing and adult mammalian brains. It was initially identified on lymphatic endothelial cells (LECs) as the E11 antigen and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38. In recent research studies, its expression has been linked with prognosis in GBM. PDPN-expressing cancer cells are highly pernicious, with a mutant aptitude to form stem cells. Such cells, on colocalization to the surrounding tissues, transition from epithelial to mesenchymal cells, contributing to the malignant carcinogenesis of GBM. PDPN can be used as an independent prognostic factor in GBM, and this review provides strong preclinical and clinical evidence supporting these claims. Full article

Breast cancer is a major global health concern as it is the primary cause of cancer death for women. Environmental radiation exposure and endogenous factors such as hormones increase breast cancer risk, and its development and spread depend on cell motility and migration. The expression of genes associated with cell motility, such as ADAM12, CYR61, FLRT2, SLIT2, VNN1, MYLK, MAP1B, and TUBA1A, was analyzed in an experimental breast cancer model induced by radiation and estrogen. The results showed that TUBA1A, SLIT2, MAP1B, MYLK, and ADAM12 gene expression increased in the irradiated Alpha3 cell line but not in the control or the malignant Tumor2 cell line. Bioinformatic analysis indicated that FLERT2, SLIT2, VNN1, MAP1B, MYLK, and TUBA1A gene expressions were found to be higher in normal tissue than in tumor tissue of breast cancer patients. However, ADAM12 and CYR61 expressions were found to be higher in tumors than in normal tissues, and they had a negative correlation with ESR1 gene expression. Concerning ESR2 gene expression, there was a negative correlation with CYR61, but there was a positive correlation with FLRT2, MYLK, MAP1B, and VNN1. Finally, a decreased survival rate was observed in patients exhibiting high expression levels of TUBA1A and MAP1B. These genes also showed a negative ER status, an important parameter for endocrine therapy. The genes related to motility were affected by ionizing radiation, confirming its role in the initiation process of breast carcinogenesis. In conclusion, the relationship between the patient’s expression of hormone receptors and genes associated with cell motility presents a novel prospect for exploring therapeutic strategies. Full article

Heavy ion radiation, prevalent in outer space and relevant for radiotherapy, is densely ionizing and poses a risk to intestinal stem cells (ISCs), which are vital for maintaining intestinal homeostasis. Earlier studies have shown that heavy-ion radiation can cause chronic oxidative stress, persistent DNA damage, cellular senescence, and the development of a senescence-associated secretory phenotype (SASP) in mouse intestinal mucosa. However, the specific impact on different cell types, particularly Lgr5⁺ intestinal stem cells (ISCs), which are crucial for maintaining cellular homeostasis, GI function, and tumor initiation under genomic stress, remains understudied. Using an ISCs-relevant mouse model (Lgr5⁺ mice) and its GI tumor surrogate (Lgr5⁺Apc^1638N/+ mice), we investigated ISCs-specific molecular alterations after high-LET radiation exposure. Tissue sections were assessed for senescence and SASP signaling at 2, 5 and 12 months post-exposure. Lgr5+ cells exhibited significantly greater oxidative stress following ²⁸Si irradiation compared to γ-ray or controls. Both Lgr5⁺ cells and Paneth cells showed signs of senescence and developed a senescence-associated secretory phenotype (SASP) after ²⁸Si exposure. Moreover, gene expression of pro-inflammatory and pro-growth SASP factors remained persistently elevated for up to a year post-²⁸Si irradiation. Additionally, p38 MAPK and NF-κB signaling pathways, which are critical for stress responses and inflammation, were also upregulated after ²⁸Si radiation. Transcripts involved in nutrient absorption and barrier function were also altered following irradiation. In Lgr5⁺Apc^1638N/+ mice, tumor incidence was significantly higher in those exposed to ²⁸Si radiation compared to the spontaneous tumorigenesis observed in control mice. Our results indicate that high-LET ²⁸Si exposure induces persistent DNA damage, oxidative stress, senescence, and SASP in Lgr5⁺ ISCs, potentially predisposing astronauts to altered nutrient absorption, barrier function, and GI carcinogenesis during and after a long-duration outer space mission. Full article

Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-Cre^ERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis. Full article

Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches. Full article

In the United States, the Federal Aviation Administration has officially classified flight crews (FC) consisting of commercial pilots, cabin crew, or flight attendants as “radiation workers” since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to the dosimetry of CIR, the role of other genotoxic exposures among FC, and whether possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to exposure to CIR in FC. We aimed to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate the risks for those who travel by air. Full article

The detrimental effects of ultraviolet radiation (UVR) on human skin are well-documented, encompassing DNA damage, oxidative stress, and an increased risk of carcinogenesis. Conventional photoprotective measures predominantly rely on filters, which scatter or absorb UV radiation, yet fail to address the cellular damage incurred post-exposure. To fill this gap, antioxidant molecules and DNA–repair enzymes have been extensively researched, offering a paradigm shift towards active photoprotection capable of both preventing and reversing UV–induced damage. In the current review, we focused on “active photoprotection”, assessing the state-of-the-art, latest advancements and scientific data from clinical trials and in vivo models concerning the use of DNA-repair enzymes and naturally occurring antioxidant molecules. Full article