Genistein Enhances TRAIL-Mediated Apoptosis Through the Inhibition of XIAP and DcR1 in Colon Carcinoma Cells Treated with 5-Fluorouracil.

Objectives: Colorectal cancer is one of the most common cancers worldwide. However, surgical intervention and chemotherapy provide only limited benefits for the recovery and survival of patients. The anticarcinogenic effect of genistein has attracted attention because epidemiological studies have shown that soybean consumption is associated with a decrease in the incidence of cancer. There are limited studies on the effects of genistein in colorectal carcinoma cells. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of genistein in SW480 and SW620 colon adenocarcinoma cells treated with 5-fluorouracil, the basis of chemotherapy, and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) ligand, the mediator of apoptosis, both alone and in combination. Materials and Methods: Cytotoxicity and genotoxicity were determined by MTT and comet assays, respectively. The apoptotic effects were evaluated by reverse transcription-polymerase chain reaction assay, with the additional use of Annexin V FITC, mitochondrial membrane potential (MMP), caspase 3, 8, and 9 activity, and reactive oxygen species (ROS) assay kits. Results: According to our findings, genistein, 5-fluorouracil, and TRAIL had synergistic apoptotic effects because of DR5 upregulation, ROS production, and DNA damage, which were mediated by increased caspase-8, and -9 activity and decreased MMP. Conclusion: The applied combinations of these compounds may contribute to the resistance problem that may occur in treating colorectal cancer, with a decrease in DcR1 and XIAP genes.

Biomonitoring of Oxidative-Stress-Related Genotoxic Damage in Patients with End-Stage Renal Disease.

Chronic kidney disease (CKD), a common progressive renal failure characterized by the permanent loss of functional nephrons can rapidly progress to end-stage renal disease, which is known to be an irreversible renal failure. In the therapy of ESRD, there are controversial suggestions about the use of regular dialysis, since it is claimed to increase oxidative stress, which may increase mortality in patients. In ESRD, oxidative-stress-related DNA damage is expected to occur, along with increased inflammation. Many factors, including heavy metals, have been suggested to exacerbate the damage in kidneys; therefore, it is important to reveal the relationship between these factors in ESRD patients. There are very few studies showing the role of oxidative-stress-related genotoxic events in the progression of ESRD patients. Within the scope of this study, genotoxic damage was evaluated using the comet assay and 8-OHdG measurement in patients with ESRD who were undergoing hemodialysis. The biochemical changes, the levels of heavy metals (aluminum, arsenic, cadmium, lead, and mercury) in the blood, and the oxidative biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were evaluated, and their relationship with genotoxic damages was revealed. Genotoxicity, oxidative stress, and heavy-metal levels, except mercury, increased significantly in all renal patients. DNA damage, 8OHdG, and MDA significantly increased, and GSH significantly decreased in patients undergoing dialysis, compared with those not having dialysis. The duration and the severity of disease was positively correlated with increased aluminum levels and moderate positively correlated with increased DNA damage and cadmium levels. In conclusion, this study revealed that the oxidative-stress-related DNA damage, and also the levels of Al and Cd, increased in ESRD patients. It is assumed that these changes may play an important role in the progression of renal damage. Approaches for reducing oxidative-stress-related DNA damage and heavy-metal load in ESRD patients are recommended.

Evaluation of genotoxicity, oxidative stress and immune parameters of auto-paint workers.

The automotive industry is a very wide area from the manufacturing of the pieces of the engine, the body, plastics to the assembly of the car. There is a chemical risk at different stages of production because of the requirement of the use of many corrosive and irritant chemicals such as paints, adhesives, acids, and bases. The aim of the study was to determine the genotoxicity, oxidative stress and immune parameters of automotive paint workers in Ankara, Türkiye. DNA damage of workers mainly responsible from the painting of the automotives were evaluated using the alkaline comet assay and the levels of some oxidative stress and immune biomarkers were also investigated. Increased lymphocyte DNA damage and also higher 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels were observed while decreased glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR) levels were found in the workers compared to their controls There were no significant differences between the study groups in the levels of interleukin (IL)- 1beta, IL-17, IL-23, Clara cell secretory protein (CC16), tumor necrosis factor-alpha (TNF-alpha), catalase (CAT), and superoxide dismutase (SOD). The results show that occupational exposure to chemicals in automotive industry may cause DNA damage in workers due to oxidative stress.

Effects of COVID-19 Disease on DNA Damage, Oxidative Stress and Immune Responses.

Coronavirus disease 2019 (COVID-19) has posed a great threat to public health and has caused concern due to its fatal consequences over the last few years. Most people with COVID-19 show mild-to-moderate symptoms and recover without the need for special treatment, while others become seriously ill and need medical attention. Additionally, some serious outcomes, such as heart attacks and even stroke, have been later reported in patients who had recovered. There are limited studies on how SARS-CoV-2 infection affects some molecular pathways, including oxidative stress and DNA damage. In this study, we aimed to evaluate DNA damage, using the alkaline comet assay, and its relationship with oxidative stress and immune response parameters in COVID-19-positive patients. Our results show that DNA damage, oxidative stress parameters and cytokine levels significantly increased in SARS-CoV-2-positive patients when compared with healthy controls. The effects of SARS-CoV-2 infection on DNA damage, oxidative stress and immune responses may be crucial in the pathophysiology of the disease. It is suggested that the illumination of these pathways will contribute to the development of clinical treatments and to reduce adverse effects in the future.

Evaluation of Oxidative Stress Parameters and Genotoxic Effects in Patients With Work-Related Asthma and Silicosis.

OBJECTIVE: To determine the mechanistic roles of oxidative stress, inflammation, and genotoxicity parameters in patients with work-related asthma (WRA) and silicosis. METHODS: Thirty-eight healthy office workers, 27 employees with a history of exposure and no disease, 24 employees with WRA, and 23 employees with silicosis were included in this study. Superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, and interleukins (IL) 17, 23, and 27 levels were measured in the serum. Genotoxic damage was evaluated by calculating the frequency of micronuclei in swab samples and 8-hydroxy-2'-deoxyguanosine in serum. RESULTS: Serum superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and IL-17, IL-23, and IL-27 levels were found to be statistically significantly higher in the exposure, WRA, and silicosis groups compared with the control group. The frequency of micronuclei in buccal epithelial cells of the patient group was found to be significantly higher than that of the control group. CONCLUSION: These results may provide information for molecular mechanisms and early diagnosis of WRA and silicosis and will be a guide for taking precautions in the early period.

Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines.

In the literature, the anticancer potential of flurbiprofen isn't fully understood. In this study, the cytotoxic, genotoxic, and apoptotic effects of flurbiprofen were evaluated in human cervical and liver cancer cells. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and it was observed that cytotoxicity increased in a concentration- and time-dependent manner. Genotoxicity was determined using alkaline Comet assay. DNA damage increased in a concentration-dependent manner. Early apoptosis was evaluated using real-time polymerase chain reaction, and it was found that apoptotic gene levels increased while antiapoptotic gene levels decreased. Late apoptosis and cell cycle analyzes were determined using flow cytometry. No evidence of late apoptosis was observed, and no significant arrest was found in the cell cycle. In conclusion, it seems that flurbiprofen has a cytotoxic, genotoxic, and apoptotic effects in both human cancer cell lines. Moreover, the findings indicate that flurbiprofen is effective at the gene level and induces apoptosis with an intracellular pathway.

Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females: DNA damage in lymphocytes and buccal cells of boron exposed females.

Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boron-poor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.