Genotoxicity and mutagenicity
Genotoxicity and mutagenicity of molybdenum(VI) and iron(III) and interactions between these microelements
Background: The aim of this study was to examine the effect of iron(III) (Fe(III)) and molybdenum(VI) (Mo(VI)) and their combinations on genotoxicity, mutagenicity, pro- and antioxidant activity in BALB/3T3 and HepG2 cells. Materials and methods: The cells were cultured in media supplemented with iron chloride or molybdenum trioxide at concentrations of 200 or 1,000 mu M. Moreover, the cells exposed to a mixture of microelements: 200 mu M of iron chloride plus 1,000 mu M of molybdenum trioxide and, in the other case, supplemented with 200 mu M of molybdenum trioxide plus 1,000 mu M of iron chloride. After 24 hours of incubation, comet, micronucleus, and Ames assays were performed. Additionally, DCFDA Cellular ROS Detection Assay, TBARS Assay, SOD Assay, Catalase Assay, and Glutathione Peroxidase Assay were performed.
Results: Additions of Fe(III) at 200 mu M plus Mo(VI) at 1,000 mu M showed synergistic effect - the increased number of comets and micronuclei in both cell lines was observed. Moreover, the number of revertants increased as well. In the case of Fe(III) at 1,000 AM plus Mo(VI) at 200 mu M, the same effect was observed. Moreover, treated cells display characteristic apoptosis in comparison to control cells. Giant and multinuclear cells were observed. In all tested microelements, the increase in number of reverse mutations was observed with and without metabolic activation. The level of reactive oxygen species and malondialdehyde (MDA) in cells increased after simultaneous exposure of cells with 200 mu M iron chloride plus 1,000 mu M molybdenum trioxide. The similar results in the case of interaction of 1,000 mu M of iron chloride plus 200 mu M of molybdenum trioxide were observed. Superoxide dismutase, catalase, and glutathione peroxidase activities decrease in a statistically significant and dose-dependent way after treatment with iron chloride and molybdenum trioxide.
Conclusion: Iron (iron(III) chloride and molybdenum (trioxide) are genotoxic and mutagenic. In our study Fe(III) and Mo(VI) show synergistic effects in genotoxicity and mutagenicity assays. Both of them can generate ROS. Moreover, Fe(III) interacts with DNA bases. These independent mechanisms can cause synergistic effects.
S. Terpilowska, and A. K. Siwicki, Genotoxicity and mutagenicity of molybdenum(VI) and iron(III) and interactions between these microelements, Trace Elements and Electrolytes, 2020, 37, 180-187.
I HAVE CORRECTED Mo(III) TO Mo(VI).
Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models
Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 mu g/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 mu m in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.
Z. Sobanska, K. Domeradzka-Gajda, M. Szparaga, J. Grobelny, E. Tomaszewska, K. Ranoszek-Soliwoda, G. Celichowski, L. Zapor, K. Kowalczyk, and M. Stepnik,Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models, Toxicology in Vitro, 2020, 68, 104931.
The Influence of Size and Phase on the Biodegradation, Excretion, and Phytotoxicity Persistence of Single-Layer Molybdenum Disulfide
The increasing applications of single-layer molybdenum disulfide (SLMoS2) pose great potential risks associated with environmental exposure. This study found that metallic-phase SLMoS2 with a nanoscale (4N-1T-SLMoS2, ~400 nm) and microscale (M-1T-SLMoS2, ~3.6 μm) diameter at 10~25 mg/L induced significant algal growth inhibition (maximum 72.7% and 74.6%, respectively), plasmolysis, and oxidative damage, but these alterations were recoverable. Nevertheless, membrane permeability, chloroplast damage, and chlorophyll biosynthesis reduction were persistent. By contrast, the growth inhibition (maximum 55.3%) and adverse effects of nano-sized semiconductive-phase SLMoS2 (4N-2H-SLMoS2, ~400 nm) were weak and easily alleviated after 96 h of recovery. 4N-1T-SLMoS2 (0.011 μg/h) and 4N-2H-SLMoS2 (0.008 μg/h) were quickly biodegraded to soluble Mo compared with M-1T-SLMoS2 (0.004 μg/h) and excreted by algae. Incomplete biodegradation of SLMoS2 (26.8%~43.9%) did not significantly mitigate their toxicity. Proteomics and metabolomics indicated that the downregulation of proteins (50.7%~99.2%) related to antioxidants and photosynthesis and inhibition of carbon fixation and carbohydrate metabolism contributed to the persistent phytotoxicity. These findings highlight the roles and mechanisms of size and phase in the persistent phytotoxicity of SLMoS2, which has potential implications for risk assessment and environmental applications of nanomaterials.
W. Zou, X. Li, C. Li, Y. Sun, X. Zhang, C. Jin, K. Jiang, Q. Zhou, and X. Hu,The Influence of Size and Phase on the Biodegradation, Excretion, and Phytotoxicity Persistence of Single-Layer Molybdenum Disulfide,Environ. Sci. Technol. 2020, 54, 19, 12295–12306.
Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models
Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 μg/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 μm in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.
Z. Sobańska, K. Domeradzka-Gajda, M. Szparaga, J. Grobelny, E. Tomaszewska, K. Ranoszek-Soliwoda, G. Celichowski, L. Zapór, K. Kowalczyk, and M. Stępnik,Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models, Toxicol In Vitro, 2020, 68, 104931.
Cytotoxicity Elicited by Molybdenum Disulphide in Different Size of Particles in Human Airway Cells
The present investigation was aimed to study the cytotoxic response induced by molybdenum disulfide in nano- (MoS2-NPs) and micro- (MoS2-MPs) size of particle in human bronchial (BEAS-2B) and alveolar (A549) cells. The cells were exposed with different particle size of MoS2 in concentrations range 1-200 mu g/mL for 24, 48, and 72 h, and then the cytotoxicity assays (MTT and NRU) was performed. Afterwards, long-term toxicity was assessed by colony forming efficiency assay (CFEA) during 10 days exposure of the cells. Both MoS2-NPs and MoS2-MPs showed similar, weak cytotoxic effects on BEAS-2B and A549 cells assessed by MTT assay, that is reduction of cell viability to approx. 60-70% at concentrations of 2.5 and 5 mu g/mL. The percentage viability remained relatively constant at this level across all concentrations above 5 mu g/mL. In long-term exposure, both MoS2 inhibited colony formation in a wider range of concentrations to 200 mu g/mL. MoS2-NPs were slightly more cytotoxic than MoS2-MPs. The data suggest the low potential hazardous nature of both MoS2 tested with an indication of higher toxicity of MoS2-NPs.
L. Zapor,Cytotoxicity Elicited by Molybdenum Disulphide in Different Size of Particles in Human Airway Cells, Rocznik Ochrona Srodowiska, 2019, 21, 794-809.
Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions
The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum , and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.
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H. R. Ghaffari, M. Yunesian, R. Nabizadeh, S. Nasseri, A. Sadjadi, F. Pourfarzi, H. Poustchi, and A. Eshraghian,Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions, Environmental science and pollution research international, 2019 26:10487–10495 https://doi.org/10.1007/s11356-019-04493-8
Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients
The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using inductively coupled plasma mass spectrometry in Korean breast cancer patients before initiation of breast cancer treatment. Korean females without breast cancer served as a control group. Trace element levels were measured in the discovery cohort (n = 287) and were validated in an independent cohort (n = 142). We further investigated possible associations between trace element levels and the presence of lymph node metastasis, distant metastasis, or triple-negative breast cancer among breast cancer patients in subgroup analyses. Serum manganese and molybdenum levels were significantly higher (p < 0.05) in breast cancer patients than in controls. Serum copper levels were significantly higher in breast cancer patients with distant metastasis, while selenium levels were significantly lower. Other trace elements were neither significantly different between breast cancer patients and controls nor between subgroups of breast cancer patients. Our study provides insights about the potential roles and impacts of trace elements through an assessment of the associations between trace elements and breast cancer.
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R. Choi, M. J. Kim, I. Sohn, S. Kim, I. Kim, J. M. Ryu, H. J. Choi, J. M. Kim, S. K. Lee, J. Yu, S. W. Kim, S. J. Nam, J. E. Lee, and S. Y. Lee,Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients, Nutrients, 2019, 11(1), 37; https://doi.org/10.3390/nu11010037
Toxicology of Molybdenum - Humans
Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults
Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose >= 7.0 mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value < 0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage. (C) 2018 Elsevier B.V. All rights reserved.
L. L. Xiao, Y. Zhou, J. X. Ma, W. W. Sun, L. M. Cao, B. Wang, C. M. Zhu, S. J. Yang, D. M. Wang, J. Yuan, and W. H. Chen,Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults, Science of the Total Environment, 2018, 627, 1327-1333.
Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls
Objective: This case control study assessed: 1) the relationship of systemic sclerosis (SSc) related to exposure to heavy metals; and 2) the risk of SSc related to occupational exposure in male and female patients.
Methods: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habit matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).
Results: SSc patients exhibited higher median levels of the following metals: antimony (p = 0.001), cadmium (p = 0.0003), lead (p = 0.02), mercury (p = 0.02), molybdenum (p = 0.04), palladium (p < 0.0001) and zinc (p = 0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p = 0.008) and platinum (p = 0:04) in male patients; and 2) antimony (p = 0.02), cadmium (p = 0.001), lead (p = 0.03), mercury (p = 0.03), palladium (p = 0.0003) and zinc (p = 0.0001) in female patients
Conclusion: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients' gender. (C) 2017 Elsevier B.V. All rights reserved.
I. Marie, J. F. Gehanno, M. Bubenheim, A. B. Duval-Modeste, P. Joly, S. Dominique, P. Bravard, D. Noel, A. F. Cailleux, J. Benichou, H. Levesque, and J. P. Goulle,Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls, Autoimmunity Reviews, 2017, 16, 223-230.
[Systemic scleroderma, also called diffusescleroderma or systemic sclerosis, is an autoimmune disease of the connective tissue. It is characterized by thickening of the skin caused by accumulation of collagen, and by injuries to small arteries. https://en.wikipedia.org/wiki/Systemic_scleroderma.
Scleroderma is caused by the immune system attacking the connective tissue under the skin and around internal organs and blood vessels. This causes scarring and thickening of the tissue in these areas.
There are two main types of scleroderma: localised scleroderma – just affects the skin systemic sclerosis – may affect blood circulation and internal organs as well as the skin.
Chronic kidney disease
High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross-sectional and longitudinal study
AIMS: Many of the secondary effects of high levels of molybdenum (Mo) overlap with symptoms commonly seen in pediatric patients with chronic kidney disease (CKD).
We measured plasma Mo levels and examined the relationship between Mo levels and kidney function.
MATERIALS AND METHODS: The study was carried out at the London Health Sciences Centre in London, Ontario, Canada with 36 children and adolescents 4 - 18 years of age with CKD. There were 1 - 6 trace element measurements (Mo and copper (Cu)) per patient. We studied the proportion of patients with abnormal trace element levels and the relationship between trace element levels and estimated glomerular filtration rate (eGFR), calculated using the Filler formula. Plasma Mo and Cu levels were measured using High Resolution Sector Field Inductively Coupled Mass Spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart program.
RESULTS: Median eGFR was 51 mL/min/1.73m2 (35, 75). Median Mo level was 2.00 microg/L (1.40, 2.88). 20 patients had at least one set of Mo levels above the published reference interval in either unit, and the results of 46% of the tests were above the interval. There was a strong negative correlation between the Mo levels and the eGFR (Spearman's r = -0.627, p. < 0.0001).
CONCLUSIONS: Our study suggests that pediatric patients with CKD have elevated plasma levels of Mo, which may cause secondary effects commonly associated with CKD. The elevated Mo levels in our center's catchment area may cause an accumulation of this trace element in patients with impaired renal function.
Yang, G., Belostotsky, V., Kobrzynski, M., Huang, S. S., and Yang, L.,High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross-sectional and longitudinal study, Clinical nephrology, 2017 88 79-85
NHS Choices: http://www.nhs.uk/Conditions/Kidney-disease-chronic/Pages/Diagnosis.aspx
The main test for kidney disease is a blood test that's used to work out how well your kidneys are working. The test measures the levels of a waste product called creatinine in your blood. Using this result, a calculation that takes into account your age, gender and ethnic group is then done to work out how many millilitres of waste your kidneys are able to filter in a minute.This measurement is known as your estimated glomerular filtration rate (eGFR).Healthy kidneys should be able to filter more than 90ml/min. You may have kidney disease if your result is lower than this.