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1.
J Toxicol Environ Health A ; 82(16): 913-919, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496443

RESUMO

Radon exposure is known to be the second most frequent cause followed by tobacco exposure for lung cancer development. In lung cancer development, microRNAs (miRNAs) play an important role in regulating various target genes associated with this disease. It is well-established that apoptosis is involved in the elimination of cancer cells. However, the mechanisms underlying chronic radon exposure induced miRNAs regulation attributed to result in carcinogenesis and subsequent activation of apoptosis is not completely understood. The aim of this study was thus to examine chronic low level radon exposure on lung miRNAs as a model for carcinogenesis induction and subsequent activation of apoptosis using human bronchial epithelial BEAS-2B cells. Quantitative real-time PCR (qRT-PCR) and flow cytometry were used to determine the miR-34a gene expression and apoptotic rate in BEAS-2B cells. Data demonstrated that chronic radon exposure up-regulated the expressions of miR-34a and enhanced cellular apoptosis in a time-dependent manner. Western blot analysis demonstrated that overexpression of the gene miR-34a enhanced apoptotic rate and elevated proapoptotic Bax protein expression accompanied by decreased protein expressions of antiapoptotic Bcl-2 and PARP-1. It is noteworthy that the apoptotic rate was elevated in BEAS-2B cells transfected with mi-R34a mimic but reduced in mi-R34a inhibitor-transfected cells. Evidence thus indicates that chronic exposure to radon produced up-regulation of miR-34a gene which subsequently enhanced apoptosis in BEAS-2B cells. The observed consequences following chronic radon exposure leading to carcinogenesis appear to involve activation of miR-34a gene.


Assuntos
Brônquios/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Células Epiteliais/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Radônio/efeitos adversos , Apoptose/efeitos dos fármacos , Humanos
2.
J Toxicol Environ Health A ; 82(15): 854-861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496446

RESUMO

Long non-coding RNAs (lncRNA) exert biological functions by interacting with RNAs, proteins, and DNA. Although lung damage associated with radon exposure was attributed to disturbances in microRNA and protein expression, the influence of radon on lncRNA is at present not known. The aim of this study was to (1) examine the effect of radon on lncRNA-mediated expression of transcription factors in mRNA in mouse lung tissue and (2) determine potential function and targets. Female BALB/c mice were divided into two groups: control and radon exposure to approximately 100,000 Bq/m3 (equivalent up to 60 working level month, WLM).RNA was extracted from lung tissue and used for high through-put lncRNA microarray analysis. A total of 1256 lncRNA transcripts were differentially expressed between the two groups of mice. Among these, the top 200 lncRNA-mRNA sets, with fold change of >2 and p-value <.05, were selected for KEGG analysis. Functional analysis via bioinformatics prediction in this study also suggested involvement of ErbB and Notch pathways in radon-induced mouse pulmonary injury. The results from immunohistochemical and Western blot analysis indicated that EbB2 and k-Ras protein expressions were significantly increased. In conclusion, approximately 1,000 dysregulated lncRNA transcripts were found in radon-exposed mice and these lncRNA may play an important role in lung damage following radon exposure. The observations in this study also suggested that ErbB2 and Notch pathways are activated and may be involved in radon-induced pulmonary toxicity.


Assuntos
Regulação da Expressão Gênica/efeitos da radiação , Pulmão/metabolismo , Pulmão/efeitos da radiação , RNA Longo não Codificante/metabolismo , Radônio/toxicidade , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
3.
J Toxicol Environ Health A ; 80(23-24): 1342-1348, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29049001

RESUMO

Changes in diurnal rhythmicity in blood pressure (BP) are associated with hypertension and consequent cardiovascular damage. The involvement of diurnal rhythmicity as a pathogenic factor in hypertension is not fully understood. Since the hormone melatonin (MLT) regulates circadian rhythm, it was also of interest to determine whether this hormone played a role in hypertension-related alterations in circadian rhythm. Thus the aim of this study was to examine the mechanisms underlying MLT-mediated antihypertension. Human umbilical vein endothelial cells were incubated with MLT under 25 kPa pressure to simulate hypertension. Vasoactive substances including endothelin (ET), angiotensin II (Ang II), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) were measured using ELISA assays. Results showed that MLT produced a significant decrease in ET at 18 and 24 h and Ang II at 18 h after treatment. In contrast, MLT significantly elevated NO levels and eNOS activity at 6, 12, 18, and 24 h, indicating that these oxidant indicators may be more sensitive to MLT-induced actions. Gene chip analysis identified 121 upregulated and 214 downregulated genes at 6 h after MLT treatment, predominantly involved in DNA replication, cell cycle regulation, amino acid metabolism, and cell cycle pathway. At 18 h, 63 upregulated and 94 downregulated genes involved in circadian entrainment, cGMP-PKG signaling pathway involved in NO synthesis, as well as secretion of renin and insulin, which are associated with BP regulation. Data suggest that the circadian antihypertensive effects of MLT might be associated with decrease in ET and Ang II, accompanied by rise in NO and eNOS and that NO and eNOS appear to be early bioindicators of hormonal effect.


Assuntos
Ritmo Circadiano , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hipertensão/metabolismo , Melatonina/metabolismo , Vasoconstritores/metabolismo , Humanos
4.
J Toxicol Environ Health A ; 80(23-24): 1331-1341, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29144200

RESUMO

The neurotoxic effects attributed to the pesticide fenvalerate (FEN) are well-established. The aim of this study was to determine whether melatonin (MLT) was able to protect against FEN-induced behavior, oxidative stress, apoptosis, and neurogenesis using zebrafish (Danio rerio) model. Zebrafish exposed to 100 µg/L FEN for 120 h exhibited decreased swimming activity accompanied by downregulated expression of neurogenesis-related genes (Dlx2, Shha, Ngn1, Elavl3, and Gfap), suggesting that neurogenesis were impaired. In addition, FEN exposure significantly elevated oxidative stress as evidenced by increased malondialdehyde levels, as well as activities of Cu/Zn superoxide dismutase (Cu/Zn SOD), catalase, and glutathione peroxidase. Acridine orange staining demonstrated that embryos treated with FEN for 120 h significantly enhanced apoptosis mainly in the brain. FEN also produced upregulation of the expression of the pro-apoptotic genes (Bax, Fas, caspase 8, caspase 9, and caspase 3) and decreased expression of the anti-apoptotic gene Bcl-2. MLT significantly attenuated the FEN-mediated oxidative stress, modulated apoptotic-regulating genes, and diminished apoptotic responses. Further, MLT blocked the FEN-induced effects on swimming behavior as well as on neurogenesis-related genes. In conclusion, MLT protected against FEN-induced developmental neurotoxicity and apoptosis by inhibiting pesticide-mediated oxidative stress in zebrafish.


Assuntos
Inseticidas/toxicidade , Melatonina/farmacologia , Nitrilas/toxicidade , Substâncias Protetoras/farmacologia , Piretrinas/toxicidade , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Natação , Poluentes Químicos da Água/toxicidade
5.
Ecotoxicol Environ Saf ; 139: 83-88, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28113115

RESUMO

This study provided distribution and health risk information of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fly ash from 4 municipal solid waste incinerators (MSWIs) in four seasons from four sites, including Zhengzhou City in Henan Province, Chuzhou City in Anhui Province, Jilin City in Jilin Province and Zibo City in Shandong Province. The toxic equivalent concentration (I-TEQ) values of PCDD/Fs ranged from 0.0707 to 0.7742ng I-TEQ/g, and no identical sequence occurred during four seasons in different sampling sites. The stabilization process might efficiently reduce the content and toxicology of PCDD/Fs in fly ash. The value of PCDD/PCDF in fly ash ranged from 0.145 to 0.787 after solidification. The characteristic index (DCI) of 2,3,4,7,8-P5CDF was 0.803 with 6.6% under 95% probability for fly ash samples discharged from MSWIs. The 95th percentile carcinogenic risks (CRs) for onsite workers were lower than the threshold value (10-5), suggesting that the cancer risk levels of PCDD/Fs in fly ash for onsite workers were acceptable. The 95th percentile non-carcinogenic risks (non-CRs) for onsite workers were lower than 1, suggesting no obvious non-carcinogenic effect was developed for onsite workers. This paper provide an overview information on the distribution of PCDD/Fs in fly ash during four seasons, and it could be used as an important fingerprint to distinguish the fly ash sources. Thus, the research could provide basic information for fly ash management in environment.


Assuntos
Poluentes Atmosféricos/análise , Benzofuranos/análise , Incineração , Dibenzodioxinas Policloradas/análise , Resíduos Sólidos/análise , Adolescente , Adulto , Idoso , China , Cidades , Cinza de Carvão/análise , Dibenzofuranos Policlorados/análise , Humanos , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Medição de Risco , Estações do Ano , Adulto Jovem
6.
Environ Health Prev Med ; 22(1): 36, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-29165116

RESUMO

BACKGROUND: Radon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear. Recently, circular RNA (circRNA), a class of endogenous non-protein coding RNAs that contain a circular loop, was found to exhibit multiple biological effects. In this study, circRNA profiles in mouse lung tissues between control and radon exposure were analyzed. METHODS: Six mice were exposed to radon at concentration of 100,000 Bq/m3, 12 h/d, for up to cumulative doses of 60 working level months (WLM). H&E staining and immunohistochemistry of caspase-3 were used to detect the damages in lung tissue. The lung tissue of control and exposed group were selected for circRNA microarray study. The circRNA/microRNA interaction was analyzed by starBase prediction software. 5 highest expressing circRNAs were selected by real-time PCR to validate the consistency in mouse lung tissue exposed to radon. RESULTS: Inflammatory reaction was found in mouse lung tissue exposed to radon, and caspase-3 expression was significantly increased. Microarray screening revealed 107 up-regulated and 83 down-regulated circRNAs, among which top 30 circRNAs with the highest fold changes were chosen for further analysis, with 5 microRNAs binding sites listed for each circRNA. Consistency of the top 5 circRNAs with the highest expressions were confirmed in mice exposed with 60WLM of radon. CONCLUSION: Mouse lung tissue was severely injured when exposed to radon through pathological diagnosis and immunohistochemical analysis. A series of differentially expressed circRNAs demonstrated that they may play an important role in pulmonary toxicity induced by radon.


Assuntos
Pulmão/efeitos dos fármacos , RNA/biossíntese , RNA/efeitos dos fármacos , Radônio/toxicidade , Animais , Caspase 3/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Camundongos , MicroRNAs , Reação em Cadeia da Polimerase , RNA Circular
7.
J Toxicol Environ Health A ; 79(9-10): 427-35, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27267825

RESUMO

The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA. Bioinformatic software was used to analyze these different mRNA and miRNA, which indicated that miR-107 and miR-494 play an important role in alpha-particles-mediated cellular malignant transformation processes. The pathways related to systemic lupus erythematosus, cytokine-cytokine receptor interaction, MAPK signaling pathway, regulation of actin cytoskeleton, and cell adhesion molecules (CAMs) were stimulated, while those of ribosome, transforming growth factor (TGF)-beta signaling pathway, and metabolic pathways were inhibited. Data suggest that miRNA and mRNA play a crucial role in alpha-particles-mediated malignant transformation processes. It is worth noting that three target genes associated with lung cancer were identified and upregulated PEG 10 (paternally expressed gene 10), ARHGAP26, and IRS1.


Assuntos
Partículas alfa/efeitos adversos , Transformação Celular Neoplásica/efeitos da radiação , Células Epiteliais/efeitos da radiação , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos da radiação , Brônquios/efeitos da radiação , Linhagem Celular , Transformação Celular Neoplásica/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Pulmonares/etiologia
8.
Environ Health Prev Med ; 20(5): 318-24, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25967734

RESUMO

OBJECTIVE: Reactive oxygen species (ROS) induced by exogenous toxicants are suggested to be involved in carcinogenesis by oxidative modification of DNA. 8-Hydroxyl-2-deoxyguanosine (8-OHdG) has been considered as a reliable biomarker for oxidative DNA damage both in vivo and in vitro studies. But the effect of smoking on oxidative damage has not yet been fully elucidated. METHODS: Wistar rats were exposed to cigarette smoke at concentrations of 20 and 60 % for 30 min, twice/day for 45 weeks. Then the histopathology of lung tissues, levels of ROS, 8-OHdG, and total antioxidant (T-AOC), expression of DNA repair enzymes, e.g. 8-oxyguaine DNA glycosylase (OGG1), and MutThomolog 1 (Oxidized Purine Nucleoside Triphosphatase, MTH1) were determined in urine, peripheral blood lymphocytes, and lung tissue. RESULTS: The results showed that long-term cigarette smoke exposure can cause obvious damages of lung tissue in rats. In addition, a significant and cigarette smoke concentration-dependent increase in ROS and 8-OHdG were observed compared with the non-exposed control rats. In contrast, the expression of OGG1 and MTH1, and T-AOC levels were obviously decreased after long-term exposure to cigarette smoke. CONCLUSION: These findings indicate that long-term exposure to cigarette smoker increases ROS levels, decreases total antioxidant capacity, and interferes DNA repair capacity that eventually induces oxidative DNA damage, which appears to play an important role in cigarette smoke-induced lung injury in rats, and determination of 8-OHdG levels might be a useful method for monitoring oxidative damage in cigarette smokers.


Assuntos
Antioxidantes/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Desoxiguanosina/análogos & derivados , Lesão Pulmonar/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Produtos do Tabaco/toxicidade , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Dano ao DNA , DNA Glicosilases/sangue , DNA Glicosilases/metabolismo , DNA Glicosilases/urina , Enzimas Reparadoras do DNA/sangue , Enzimas Reparadoras do DNA/urina , Desoxiguanosina/sangue , Desoxiguanosina/metabolismo , Desoxiguanosina/urina , Relação Dose-Resposta a Droga , Linfócitos/efeitos dos fármacos , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/urina , Fumaça/efeitos adversos
9.
Wei Sheng Yan Jiu ; 43(1): 16-21, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24564105

RESUMO

OBJECTIVE: To study the effects of nano-selenium (NSe) on cognition performance of mice exposed to 1800 MHz radiofrequency fields (RF). METHODS: Male mice were randomly divided into four groups, control and nano-Se low, middle and high dose groups (L, M, H). Each group was sub-divided into three groups, RF 0 min, RF 30 min and RF 120 min. Nano-se solution (2, 4 and 8 microg/ml) were administered to mice of L, M, H groups by intra-gastric injection respectively, 0.5 ml/d for 50 days, the conctral group were administered with distilled water. At the 21st day, the mice in RF subgroup were exposed to 208 microW/cm2 1800 MHz radiofrequency fields (0, 30 and 120 min/d respectively) for 30 days. The cognitive ability of the mice were tested with Y-maze. Further, the levels of MDA, GABA, Glu, Ach and the activities of CAT and GSH-Px in cerebra were measured. RESULTS: Significant impairments in learning and memory (P < 0.05) were observed in the RF 120 min group, and with reduction of the Ach level and the activities of CAT and GSH-Px and increase of the content of GABA, Glu and MDA in cerebrum. NSe enhanced cognitive performance of RF mice, decreased GABA, Glu and MDA levels, increased Ach levels, GSH-Px and CAT activities. CONCLUSION: NSe could improve cognitive impairments of mice exposed to RF, the mechanism of which might involve the increasing antioxidation, decreasing free radical content and the changes of cerebra neurotransmitters.


Assuntos
Transtornos Cognitivos/prevenção & controle , Cognição/efeitos da radiação , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/análise , Selênio/farmacologia , Animais , Antioxidantes/metabolismo , Cognição/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos da radiação , Nanopartículas Metálicas , Camundongos , Neurotransmissores/metabolismo , Substâncias Protetoras/farmacologia , Ondas de Rádio
10.
J Toxicol Environ Health A ; 76(2): 107-19, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23294299

RESUMO

Radon and its progeny are confirmed to be type I carcinogenic agents accounting for increased risks in 10% of observed lung cancers globally. However, the underlying carcinogenic mechanisms are largely unknown. In the present study, BEAS2B cells were directly exposed twice to 20,000 Bq/m(3) radon gas for 20 min once (first passage) and subsequently 10 times (fifth passage). The fifth-passage cells were then subcultured for 1 and 20 generations (named Rn5-1 and Rn5-20, respectively). Molecular mechanisms indicative of malignant transformation were assessed by determination of apoptosis, seroresistance, and microRNA (miRNA) expression profiles. The microRNA profiles were used to assess the functional annotations of the target genes. Data indicated an increased seroresistance and colony efficiency on soft agar, and enhanced apoptosis resistance in the Rn5-20 cells with significant differential expressions in some miRNA, including hsa-miR-483-3p, hsa-miR-494, hsa-miR-2115*, hsa-miR-33b, hsa-miR-1246, hsa-miR-3202, hsa-miR-18a, hsa-miR-125b, hsa-miR-17*, and hsa-miR-886-3p. Functional annotation demonstrated that these miRNA target genes were predominantly involved in the regulation of cell proliferation, differentiation, and adhesion during the process of malignant transformation, which is associated with signal pathways such as mitogen-activated protein kinase (MAPK), Int and Wg (Wnt), reactive oxygen species (ROS), nuclear factor κB (NF-κB), and other genes regulating cell cycles.


Assuntos
Poluentes Radioativos do Ar/toxicidade , Carcinógenos Ambientais/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , MicroRNAs/metabolismo , Radônio/toxicidade , Transcriptoma/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
11.
Reprod Biomed Online ; 25(5): 536-42, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22999556

RESUMO

Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) may play an important role in male reproduction. So far, such data for humans are not available. This study used single-nucleotide polymorphisms (SNP) to examine the association between CLOCK and semen quality in a human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 men with idiopathic infertility by SNP genotyping assays and computer-aided sperm analysis. Subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume (P=<0.001 and 0.001, respectively) compared with the TT genotype. Subjects carrying the rs3749474 CC genotype had significantly lower sperm number per ejaculate (P=0.026) and sperm motility (P=0.021) than TT genotype carriers. rs1801260 TC genotype carriers had significantly lower sperm motility compared with the TT genotype (P=0.028). For the rs3817444 genotypes, CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype (P=0.022 and 0.001, respectively). The findings suggest, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility. The gene encoding the circadian locomotor output cycles kaput protein (CLOCK) functions as an important positive enhancer of the circadian system. The observations reported in recent experimental animal studies suggested that CLOCK may play an important role in male reproduction. So far, such data for humans are not available. In this study, single-nucleotide polymorphisms (SNP) were used to examine the association between CLOCK and semen quality in human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 males with idiopathic infertility by SNP genotyping assays and computer-assisted semen analysis. The results showed that the subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume compared with the TT genotype. For subjects carrying the CC genotype, sperm number per ejaculate and sperm motility were significantly lower compared with TT genotype carriers. The rs1801260 TC genotype carriers also had significantly lower sperm motility compared with the TT genotype. For the rs3817444 genotypes, the CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype. The findings suggested, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility.


Assuntos
Proteínas CLOCK/genética , Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Adulto , China/etnologia , Genótipo , Humanos , Masculino , Análise do Sêmen
12.
Artigo em Inglês | MEDLINE | ID: mdl-22852813

RESUMO

Despite the fact that animal and human epidemiological studies confirmed a link between radon exposure in homes and increased risk of lung cancer in general population, other types of cancers induced by radon, such as leukemia, have not been consistently demonstrated. The aim of this review was to summarize data published thus far from ecological and case-control studies in exposed populations, taking into account radon dose estimation and evidence of radon-induced genotoxicity, in an effort to clarify the correlation between home radon exposure and incidence of childhood leukemia. Among 12 ecological studies, 11 reported a positive association between radon levels and elevated frequency of childhood leukemia, with 8 being significant. In conjunction with ecological studies, several case-control studies on indoor radon exposure and childhood leukemia were examined, and most investigations indicated a weak association with only a few showing significance. A major source of uncertainty in radon risk assessment is radon dose estimate. Methods for radon exposure measurement in homes of children are one of the factors that affect the risk estimates in a case-control study. The effects of radon-induced genetic damage were studied both in vitro and in vivo using genetic endpoints including chromosomal aberration (CA), micronuclei (MN) formation, gene mutation, and deletions and insertions. By applying a meta-analysis, an increased risk of childhood leukemia induced by indoor radon exposure was noted for overall leukemia and for acute lymphoblastic leukemia (ALL). Data thus indicated an association between environmental radon exposure and elevated leukemia incidence, but more evidence is required in both human investigations and animal mechanistic research before this assumption may be confirmed with certainty.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Exposição Ambiental/efeitos adversos , Leucemia Induzida por Radiação/epidemiologia , Radônio/toxicidade , Animais , Criança , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Humanos , Incidência , Leucemia Induzida por Radiação/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Doses de Radiação , Radônio/análise , Medição de Risco , Fatores de Risco
13.
J Toxicol Environ Health A ; 75(12): 707-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22757675

RESUMO

The lack of apoptotic pathways may lead to undesirable cell survival and proliferation, which are recognized hallmarks of cancer. It is well known that exposure to cigarette smoke induces DNA lesions in pulmonary cells. At present, it is not fully elucidated whether these lesions are repaired to restore normal functions or induce apoptosis. In order to examine the role of apoptosis in smoking-induced effects, immortalized human bronchial epithelial cells (BEAS-2B) were exposed to cigarette smoke and examined for parameters associated with apoptosis and neoplastic transformation. Our results indicated a significant reduction in apoptosis and enhanced neoplastic transformation and decreased mitochondrial membrane potential Δψm of mitochondria compared to control cells. Time-course experiments revealed increased aberrant methylation of CpG islands of RAS-associated domain family protein 1A (RASSF1A) and O (6)-methylguanine-DNA-methyltransferase (MGMT). The activities were downregulated and repair of DNA adducts was inhibited. Our observations suggested that although cigarette smoke-induced damage in BEAS-2B cells after chronic exposure is not necessarily lethal, as evidenced by cell viability, the protein expression levels of caspase-3 showed a decrease in the S20 passage (metaphase) but subsequently increased from S30 to S40 (anaphase). Survivin expression was significantly changed in S5 cells, and this rise was maintained until S40. Our data suggest that the potency of cigarettes as carcinogens may be due to their ability to induce aberrant gene expression and failure to trigger apoptosis leads to subsequent neoplastic transformation.


Assuntos
Apoptose/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Mucosa Respiratória/citologia , Fumar/efeitos adversos , Animais , Brônquios/citologia , Brônquios/efeitos dos fármacos , Linhagem Celular , Metilação de DNA/efeitos dos fármacos , Células Epiteliais/citologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/induzido quimicamente , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
J Toxicol Environ Health A ; 75(18): 1120-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22891885

RESUMO

Radiofrequency fields (RF) at 1800 MHz are known to affect melatonin (MEL) and testosterone in male rats, but it remains to be determined whether RF affected circadian rhythm of these plasma hormones. Male Sprague-Dawley rats were exposed to 1800-MHz RF at 208 µw/cm² power density (SAR: 0.5762 W/kg) at different zeitgeber (ZT) periods of the day, including 0 (ZT0), 4 (ZT4), 8 (ZT8), 12 (ZT12), 16 (ZT16), and 20 (ZT20) h. RF exposure was 2 h/d for 32 d. From each rat, the concentrations of plasma MEL and testosterone were determined in plasma after RF exposure and compared with controls. The results confirmed the existence of circadian rhythms in the synthesis of MEL and testosterone, but revealed an inverse relationship in peak phase of these rhythms. These rhythms were disturbed after exposure to RF, with the effect being more pronounced on MEL than testosterone. The most pronounced effect of RF exposure on MEL and testosterone appears to be in rats exposed to RF at ZT 16 and ZT0 h, respectively. Data suggest that regulation of testosterone is controlled by MEL and that MEL is more sensitive to RF exposure.


Assuntos
Ritmo Circadiano/efeitos da radiação , Melatonina/sangue , Ondas de Rádio/efeitos adversos , Testosterona/sangue , Irradiação Corporal Total/efeitos adversos , Algoritmos , Animais , Cinética , Masculino , Melatonina/metabolismo , Glândula Pineal/metabolismo , Glândula Pineal/efeitos da radiação , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testículo/efeitos da radiação , Testosterona/metabolismo
15.
J Toxicol Environ Health A ; 75(12): 694-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22757673

RESUMO

Oxidative damage can be induced by many environmental stressors. 8-Hydroxydeoxyguanosine (8-OHdG) has been used as a biomarker of oxidative DNA damage in both in vitro and in vivo studies. In the present study, Wistar rats were exposed to radon gas at a concentration of 100,000Bq/m(3) for 12 h/d for 30, 60, and 120 d, equivalent to cumulative doses of 60, 120, and 240 working level months (WLM), respectively. Changes in levels of 8-OHdG, reactive oxygen species (ROS), and total antioxidant (T-AOC), as well as expressions of some DNA repair enzymes such as 8-oxoguanine DNA glycosylase (OGG1) and MutT homolog 1 (oxidized purine nucleoside triphosphatase, MTH1), were determined in rat urine, peripheral blood lymphocytes, and lung after exposure to radon. The results revealed an increase in 8-OHdG and ROS levels, a decrease in T-AOC levels, and reduced OGG1 and MTH1 expression levels. The elevated amount of 8-OHdG in urine or lymphocytes was positively correlated with the cumulative exposure dose, whereas OGG1 and MHT1 expression levels in lung were inversely correlated with cumulative exposure dose. These findings indicate that oxidative damage induced by radon may be involved in radon-induced carcinogenesis.


Assuntos
Poluentes Radioativos do Ar/toxicidade , Antioxidantes/metabolismo , Desoxiguanosina/análogos & derivados , Estresse Oxidativo/efeitos da radiação , Radônio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores , Líquido da Lavagem Broncoalveolar/citologia , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Reparo do DNA , Enzimas Reparadoras do DNA/metabolismo , Desoxiguanosina/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Pulmão/metabolismo , Masculino , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
16.
ACS Appl Mater Interfaces ; 14(16): 18110-18119, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35435678

RESUMO

Temperature is one of the key parameters for activity of cells. The trade-off between sensitivity and biocompatibility of cell temperature measurement is a challenge for temperature sensor development. Herein, a highly sensitive, biocompatible, and degradable temperature sensor was proposed to detect the living cell extracellular environments. Biocompatible silk materials were applied as sensing and packing layers, which endow the device with biocompatibility, biodegradability, and flexibility. The silk-based temperature sensor presented a sensitivity of 1.75%/°C and a working range of 35-63 °C with the capability to measure the extracellular environments. At the bending state, this sensor worked at promising response of cells at different temperatures. The applications of this developed silk material-based temperature sensor include biological electronic devices for cell manipulation, cell culture, and cellular metabolism.


Assuntos
Nanofibras , Seda , Materiais Biocompatíveis , Eletrônica , Temperatura
17.
J Radiat Res ; 63(5): 706-718, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-35791446

RESUMO

Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process.


Assuntos
Poluentes Radioativos do Ar , Carcinógenos , MicroRNAs , Radônio , Pele , Poluentes Radioativos do Ar/toxicidade , Animais , Carcinógenos/toxicidade , Ácido Graxo Sintase Tipo I/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Neoplasias Induzidas por Radiação/metabolismo , Proteômica , Radônio/toxicidade , Pele/lesões , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/induzido quimicamente
18.
Chemosphere ; 286(Pt 2): 131802, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426134

RESUMO

BACKGROUND: Spontaneous abortion (SAB) brings serious physical and psychological sequelae to women and their families. Though a growing body of individual studies have suggested the possible linkage between chronic particulate matter (PM) exposure and risks of SAB, the provided results were rather contradictory. We therefore performed an evidence-based meta-analysis. METHODS: We systematically searched the PubMed, EMBASE and Web of Science databases for available studies published before February 1, 2021 which reported associations between PM exposure and SAB. Corresponding models were applied to combine relative risks (RRs) and their confidence intervals (CIs) from eligible studies according to heterogeneity test. The GRADEpro app was used to evaluate the certainty of evidence. Sensitivity analyses and a publication bias assessment were also utilized to determine the stability of results. RESULTS: Of the initial 2358 citations, 6 papers examining the chronic effects of PM exposure were deemed eligible and a total population of approximately 723,000 was observed. Pooled RR for SAB risks associated with a 10 µg/m3 increase in fine particulate matter (PM2.5) and particulate matter ≤ 10 µm in aerodynamic diameter (PM10) were 1.20 (95%CI: 1.01-1.40) and 1.09 (95%CI: 1.02-1.15), respectively. The GRADE results of PM2.5 and PM10 were both categorized as "moderate" certainty evidence. CONCLUSION: Our findings revealed a significant increase of SAB hazards related with maternal PM exposure, and this study may therefore provide new evidence for personal protection to improve reproductive health.


Assuntos
Aborto Espontâneo , Poluentes Atmosféricos , Poluição do Ar , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Material Particulado/análise , Gravidez
19.
J Toxicol Environ Health A ; 73(7): 499-506, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20391129

RESUMO

This study was designed to construct and identify the subtracted cDNA library in peripheral blood cells of BALB/c mice and tracheal-bronchial epithelial cells of Wistar rats following exposure to radon inhalation. Two groups of the animals were exposed in a radon chamber at an accumulative dose of 100 WLM, while control animals were housed in a room at a background dose of 1 WLM. To construct a subtracted cDNA library enriched with differentially expressed genes, the SMART technique and suppression subtractive hybridization (SSH) assay were performed. The obtained forward and reverse cDNA fragments were directly inserted into a pMD-18 vector and transformed into Escherichia coli JM109. In total, 593 white bacterial clones were selected from both forward- and reverse-subtracted libraries. Among them, 81 clones were chosen for their differential expressions based on reverse Northern blot. Portions of these cDNA clones were also verified by a quantitative real-time polymerase chain reaction (PCR). The screening resulted in 14 upregulative and 8 downregulative known function/annotation genes, which were revealed to be functionally related to cell proliferation, cell oxidative and DNA damage, apoptosis, and tumor promotion. Access numbers were obtained from the GenBank for 11 unknown expressed sequence tags (EST). Analysis of biological roles of these cDNA fragments may provide further insight into mechanisms underlying adverse molecular events induced by high-dose radon exposure.


Assuntos
Células Sanguíneas/efeitos da radiação , Células Epiteliais/efeitos da radiação , Expressão Gênica/efeitos da radiação , Radônio/toxicidade , Mucosa Respiratória/efeitos da radiação , Animais , Biomarcadores/metabolismo , Células Sanguíneas/metabolismo , Brônquios/citologia , Brônquios/metabolismo , Brônquios/efeitos da radiação , Relação Dose-Resposta à Radiação , Regulação para Baixo/efeitos da radiação , Células Epiteliais/metabolismo , Biblioteca Gênica , Exposição por Inalação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Traqueia/citologia , Traqueia/metabolismo , Traqueia/efeitos da radiação , Regulação para Cima/efeitos da radiação
20.
J Toxicol Environ Health A ; 73(7): 507-13, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20391130

RESUMO

Exposure of humans simultaneously to microwave and gamma-ray irradiation may be a commonly encountered phenomenon. In a previous study data showed that low-dose microwave radiation increased the survival rate of mice irradiated with 8Gy gamma-ray; however, the mechanisms underlying these findings remain unclear. Consequently, studies were undertaken to examine the effects of microwave exposure on hematopoietic system adversely altered by gamma-ray irradiation in mice. Preexposure to low-dose microwaves attenuated the damage produced by gamma-ray irradiation as evidenced by less severe pathological alterations in bone marrow and spleen. The protective effects of microwaves were postulated to be due to up-expression of some hematopoietic growth factors, stimulation of proliferation of the granulocyte-macrophages in bone marrow, and inhibition of the gamma-ray induced suppression of hematopoietic stem cells/hematopoietic progenitor cells. Data thus indicate that prior exposure to microwaves may be beneficial in providing protection against injuries produced by gamma-ray on the hematopoietic system in mice.


Assuntos
Raios gama/efeitos adversos , Sistema Hematopoético/efeitos da radiação , Micro-Ondas/uso terapêutico , Lesões Experimentais por Radiação/radioterapia , Proteção Radiológica , Animais , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Células Progenitoras de Granulócitos e Macrófagos/efeitos da radiação , Sistema Hematopoético/metabolismo , Sistema Hematopoético/patologia , Interleucina-3/metabolismo , Masculino , Camundongos , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Baço/patologia , Baço/efeitos da radiação
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