ABSTRACT
Resumo O agrotóxico malathion vem sendo amplamente utilizado no mundo em programas de controle de arboviroses e em 2015 foi classificado pela Agência Internacional para Pesquisas em Câncer (IARC) como provável agente carcinogênico para seres humanos. Este trabalho objetivou a sistematização das evidências dos efeitos carcinogênicos e mutagênicos associados à exposição do malathion e seus análogos, malaoxon e isomalathion. A busca foi realizada nas bases de dados TOXLINE, PUBMED e SCOPUS por artigos originais publicados de 1983 a 2015. Do total de 273 artigos elegíveis, foram selecionados 73. Os resultados dos estudos in vitro e in vivo evidenciaram danos genéticos e cromossômicos provocados pelo malathion; os estudos epidemiológicos evidenciaram associações significativamente positivas para cânceres de tireóide, de mama, e ovariano em mulheres na menopausa. Estas evidências do efeito carcinogênico do malathion devem ser considerados diante de sua utilização em programas de controle de arboviroses.
Abstract Malathion has been widely used worldwide in arbovirus control programs. In 2015, it was classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen to humans. This work aimed to systematize the evidence of the carcinogenic and mutagenic effects associated with the exposure of malathion and its analogs, malaoxon and isomalathion. The search was carried out in Toxline, PubMed and Scopus databases for original papers published from 1983 to 2015. In all, 73 papers were selected from a total of 273 eligible papers. The results of in vitro and in vivo studies showed mainly genetic and chromosomal damages caused by malathion. The epidemiological studies evidenced significant positive associations for thyroid, breast, and ovarian cancers in menopausal women. This evidence of the carcinogenic effect of malathion should be considered before its use in arbovirus control programs.
Subject(s)
Humans , Female , Malathion/toxicity , Mutagens/toxicityABSTRACT
Introdução: o óleo de copaíba é o composto extraído do tronco da copaibeira (Copaifera sp.) que tem sido utilizado na medicina popular desde a chegada dos portugueses ao Brasil. Objetivo: o objetivo deste estudo foi avaliar possíveis efeitos carcinogênicos e/ ou anticarcinogênicos do óleo de copaíba (Copaifera officinalis L.), por meio do teste para detecção de clones de tumores epiteliais (warts) em Drosophila melanogaster. Metodologia: foram preparadas três soluções de óleo de copaíba, nas proporções de 0,5%, 1% e 2%. Nessas soluções foram cultivadas Drosophilas melanogaster expostas simultaneamente à doxorrubicina na concentração de 0,4 mM, agente conhecidamente cancerígeno, também utilizado como controle positivo na presente pesquisa. Para controle negativo foi utilizado Tween 80 (1%). O tratamento foi realizado com todas as larvas descendentes do cruzamento de fêmeas wts/ TM3 com machos mwh/mwh. Resultados: o óleo de copaíba apresentou atividade carcinogênica quando utilizado isoladamente na concentração 2%, visto que houve aumento estatisticamente significativo (p ≤ 0,05) na frequência de tumores em comparação com o controle negativo. Além disso, evidenciou-se potencialização do efeito carcinogênico da doxorrubicina nas concentrações 0,5% e 1%, uma vez que houve um aumento estatisticamente significativo (p ≤ 0,05) na frequência de tumores nessas concentrações, quando associadas à DXR, em comparação com o controle positivo. Conclusão: os resultados evidenciaram o efeito carcinogênico isolado do óleo de copaíba, bem como seu efeito potencializador quando associado à doxorrubicina.
Introduction: the copaiba oil is a compound extracted from the trunk of the copaiba tree (Copaifera sp.) that has been used in popular medicine since the arrival of the Portuguese in Brazil. Purpose: this study aimed to evaluate the possible carcinogenic and/ or anticarcinogenic effects of the copaiba oil (Copaifera officinalis L.) through the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster. Methodology: three solutions of copaiba oil were prepared in the proportions 0,5%, 1% and 2%. In these solutions were cultivated Drosophilas melanogaster previously exposed to doxorubicin at a 0.4 mM concentration, admittedly carcinogenic agent, which was also used for positive control in the present research. For negative control Tween 80 (1%) was used. The treatment was performed on all larvae descendant of the crossing of females wts/TM3 with males mwh/mwh. Results: the results showed that the copaiba oil presented carcinogenic activity when used in isolation at the concentration of 2%, seeing that there was a statistically significant increase (p ≤ 0,05) in tumor frequency in comparison to the negative control. Moreover, there was a potentiation of doxorubicin's carcinogenic effect at concentrations 0,5% and 1%, since there was a statistically significant increase (p ≤ 0,05) of tumor frequency in these concentrations, when associated to DXR, in comparison to the positive control. Conclusion: the results evidenced the isolated carcinogenic effect of copaiba oil, as well as its potentiating effect when associated with doxorubicin
Subject(s)
Animals , Male , Female , Plants, Medicinal , Doxorubicin , Drosophila melanogaster , DipteraABSTRACT
BACKGROUND:Many scholars have experimental y confirmed the obvious effect of mesenchymal stem cells to repair radiation injury. OBJECTIVE:To preliminarily investigate the mechanism of human umbilical cord mesenchymal stem cells promoting the healing of combined radiation-wound skin injury and whether they possess tumorigenicity in vitro. METHODS:Fifteen Sprague-Dawley rats were randomly divided into three groups, five rats in each group. The right buttock of rats (2.5 cm×2.0 cm) was irradiated with 40 Gyβ-rays produced by a linear accelerator, in which a round wound with a diameter of 1.5 cm was made. After 12 hours of modeling, human umbilical cord mesenchymal stem cells at three concentrations (5.0×106, 1.0×107 and 2.0×107 ) were injected through tail vein of rats, and luciferin (20 mg/kg) was injected intraperitoneal y. celldistribution in vivo was traced using IVIS in vivo imaging system. The ability of human umbilical cord mesenchymal stem cells to form colonies was observed using the colony formation assay with soft agar. RESULTS AND CONCLUSION:Human umbilical cord mesenchymal stem cells injected through tail vein of rats were mostly gathered in the lungs. cells were accumulated in the injured site of rats injected with 2.0×10 7 human umbilical cord mesenchymal stem cells;however, the fluorescence signal was not observed in the injured site of rats injected with 5.0×106 and 1.0×107 human umbilical cord mesenchymal stem cells. The other results indicated human umbilical cord mesenchymal stem cells of low dose, medium dose and high dose had no colony formation on soft agar, but the tumor cells had a great ability to form colony. These findings indicate that human umbilical cord mesenchymal stem cells promote healing combined radiation-wound skin injury by local migration and exhibit no tumorigenicity in vitro in a short period.
ABSTRACT
BACKGROUND:Stem celltumorigenicity is a practical issue concerning stability in the clinical application of stem cells. Therefore, it is particularly important to clear whether stem cells have tumorigenic ability or not. Nude mice occupy an increasingly important position in oncology, immunology, and safety evaluation of drugs and biological products. OBJECTIVE:To observe the tumorigenicity of neural stem cells and mesenchymal stem cells in Balb/c nude immunodeficient mice. METHODS:Balb/c nude mice were randomly divided into control group, negative group, positive group, neural stem cellgroup and mesenchymal stem cellgroup. HepG-2 cells, RPE cells, passage 4 neural stem cells and mesenchymal stem cells were injected subcutaneously into nude mice from different groups, respectively. After 12 weeks of injection, anatomical observation was performed to detect the tumor formation in the transplantation site. Meanwhile, soft agar colony formation assay was applied to investigate neural stem celland mesenchymal stem cellclone in vitro. RESULTS AND CONCLUSION:After 12 weeks of injection, the tumorigenicity study results showed that no tumor developed in the transplantation site in the control group, negative group, neural stem cellgroup and mesenchymal stem cellgroup. Histopathologic examinations also showed no abnormality in these groups. Soft agar colony formation assay showed in soft agar resistance medium, neural stem cells and mesenchymal stem cells did not exhibit clone ability. These findings indicate that neural stem cells and mesenchymal stem cells undergoing short-term passages have no tumorigenic growth.
ABSTRACT
Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Gastric Mucosa/chemistry , Helicobacter pylori , Precancerous Conditions/chemistry , Receptors, Immunologic/analysis , Stomach Neoplasms/chemistry , Biomarkers/analysis , Biopsy , Cyclin D1/analysis , Gastric Mucosa/microbiology , /analysis , Helicobacter Infections/metabolism , Immunohistochemistry , Mucin-1/analysis , beta Catenin/analysisABSTRACT
BACKGROUND:A large amount of studies have confirmed that synovial mesenchymal stem cells have the similarity in cellmorphology, immune phenotype, colony forming ability and differentiation potential with bone marrow mesenchymal stem cells. But bone marrow mesenchymal stem cells are better than synovial mesenchymal stem cells in the ability to differentiate into cartilages. OBJECTIVE:To discuss the possibility of using synovial mesenchymal stem cells as seed cells for meniscal tissue engineering. METHODS:The synovial mesenchymal stem cells were isolated from rabbit synovial tissues with limiting dilution monoclonal culture method, and then the cells were purified. The morphology, ultrastructure, molecular phenotype, proliferation kinetics, karyotype and tumorigenicity of the in vitro cultured cells were analyzed. RESULTS AND CONCLUSION:The synovial mesenchymal stem cells isolated from the rabbit synovial cells had high proliferation capacity during in vitro monolayer culture. The synovial mesenchymal stem cells grew to peak at 6 days, and the doubling time was (30.2±2.4) hours. Flow cytometry results showed the synovial mesenchymal stem cells could express some molecular makers of mesenchymal stem cells, such as CD44 and CD90. DNA contents check, karyotype test and oncogenicity test confirmed isolated and purified synovial mesenchymal stem cells were the normal diploid cells without tumorigenicity, so the cells can be used as seed cells for meniscal tissue engineering.
ABSTRACT
Objective: To investigate the possible oncogenicity of bone marrow stromal stem cells (BMSCs) transplanted into brain and its underlying mechanism. Methods: The contralateral hemiplegia became gradually worse in three Sprague-Dawley rats among twenty rats after intracerebral transplantation with BMSCs. The intracerebral space occupying lesions were examined by MRI, and the life span of these rats was observed and recorded. The tumor tissues were obtained after the three rats were sacrificed. The telomerase activity was detected by telemeric repeat amplification protocol (TRAP)- PCR-enzyme-linked immunosorbent assay (ELISA). The expressions of proliferating cell nuclear antigen (PCNA), nestin and glial fibrillary acidic protein (GFAP) were detected by immunohistochemistry. The relative expression levels of epidermal growth factor receptor(EGFR), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) proteins in intracerebral tumor tissues and normal tissues were examined by Western blotting. Results: Of twenty rats, three rats displayed left hemiplegia which was continuously getting worse, and the life spans of the three rats were 129, 174 and 187 d, respectively. The result of TRAP-PCR-ELISA showed that the telomerase activity of intracerebral tumor tissues was higher than that of intracerebral normal tissues. The expressions of PCNA and nestin proteins in intracerebral tumor tissues were both higher but the expression of GFAP was lower than those of intracerebral normal tissues. The results of Western blotting showed that among three rats with intracerebral normal tissues, the expression level of EGFR protein was increased in one rat while the expression level of VEGF protein was increased in two rats. There was no significant difference in the expression of MMP-9 protein among the three rats. Conclusion: The telomerase activity and the ability of cell proliferation of BMSCs can be enhanced and the activation of oncogenes can be observed after long-term cell culture in vitro, and these findings suggest that the tumorigenesis potential can be induced after intracerebral transplantation with MSCs. Copyright© 2011 by TUMOR.
ABSTRACT
Objective: To establish a chronic malignant transformation model of immortalized human bronchial epithelial cell line BEP-2D by low dose cigarette smoke condensate (simulating smoking environment). Methods: The chronic dose of cigarette smoke condensate was determined by MTT assay and the colony formation test of BEP-2D cells. BEP-2D cells were exposed to cigarette smoke condensate once or for multiple times; unexposed cells were taken as control. The malignant tendency of BEP-2D cells was identified by anti-serum experiment and the malignant features of transformed BEP-2D cells were identified by semisolid agar culture. The differentiation ability of BEP-2D cells in anti-serum experiment and the colony forming rates of BEP-2D cells were compared between different groups. Results: The BEP-2D cells were exposed to 0.5, 1 and 2 μl/ml of cigarette smoke condensate once or for multiple times and were cultured for 25 generations; the differentiation abilities of BEP-2D cells(the 25th generation) was significantly different between the cigarette smoke condensate exposed groups (at 0.5, 1 and 2 μl/ml) and the normal control group (P<0.05). The cell malignant transformation model was successfully established in the cells of the 38th generation; the cells had multi-layer growth and had no contacting inhibition, with chromosome abnormality. The colony forming rates in the semisolid agar culture test was significantly higher in all smoke condensate exposed groups than in control group(P<0.05). The dose-response relationship showed a good linear correlation (r=0.969, y=42x, P<0.05). Conclusion: The malignant transformation of immortalized human bronchial epithelial cells can be successfully induced by cigarette smoke condensate at 0.5-2 μl/ml, which offers an ideal model for simulating smoking environment induced chronic malignant transformation.
ABSTRACT
Objective:To isolate cancer stem cells from cervical carcinoma and to identify their biological characteristics. Methods:Tumor specimens were obtained from 19 cervical cancer patients at stages ⅠA-ⅡB. Primary cells were cultured in tumor sphere medium (TSM) after mechanical dissociation combined with enzymatic digestion. A series of assays were used to identify the characteristics of the sphere forming cells derived from primary culture. Colony formation was observed by limiting dilution method. MTT assay was used to assess proliferation inhibition by paclitaxel and doxorubicin. Cell surface markers were analysed by fluorescence-activated cell sorter (FACS). The expression of stemness-related genes, drug resistance-related genes, and oncogenes were detected by RT-PCR and Western blotting. Tumorigenicity was evaluated by subcutaneous injection of 1×10~5 sphere-forming cells into nude mice. The tumor formation capability was recorded and pathological classification was performed.Results:After 10 to 15 d culture, the formation of non-adherent spheres could be observed in 8 out of 19 primary tumor cells. The formation ratio was increased with the increase in clinical staging. Sphere-forming cells had colony formation capability. Paclitaxel (100 nmol/L) and doxorubicin (100 nmol/L) inhibited the proliferation of these cells by (77.65±6.46)% and (48.00±7.15)%, respectively. The difference was significant (P<0.01). FACS detection results indicated the phenotypes of sphere-forming cells were CD34~-CD105~-CD44~+CK17~+. RT-PCR detection indicated that spheres expressed stemness-related genes (Oct4 and Piwil2), drug resistance gene ABCG2, and oncogenes (c-myc, sox-2 and stat3). Western blotting further indicated stemness-related protein (Oct4 and Piwil2) expression in spheres. Tumors appeared in all animals at 12 weeks after subcutaneous injection of 1×10~5 sphere forming cells and exhibited a high degree of similarity with the primary tumor in cervical cancer patients. Conclusion:Human cervical cancer stem cells were successfully isolated,which provided a useful model for individualized therapy and evaluation of the therapeutic efficacy for cervical cancer patients.
ABSTRACT
A rápida oxidação da matéria orgânica dos solos tropicais é mais uma evidência da grande vantagem do uso de biossólidos como condicionadores, capazes de melhorar as características físicas, químicas e biológicas do solo com grandes reflexos na produtividade agrícola. Portanto, o presente projeto objetivou averiguar o potencial genotóxico e cancerígeno dos lotes do Lodo de Estação de Tratamento de Esgoto (LETE) gerado em uma ETE prédefinida na região da bacia hidrográfica Piracicaba, Capivari e Jundiaí (PCJ1). Estes dados poderão fornecer subsídios para a avaliação do risco das populações humanas e o meio ambiente expostas ao LETE. Foram utilizados 140 ratos Wistar machos com 8 semanas de idade, expostos, via ração, a concentrações de 10.000 e 50.000ppm de LETE, durante 6 e 8 semanas, com os iniciadores DEN (N-dietilnitrosamina) e DMH (1,2- dimetilhidrazina), conforme citado nos respectivos protocolos (Figuras 4 e 5). A avaliação toxicológica do lodo de esgoto desenvolvida pelo Núcleo de Avaliação do Impacto Ambiental Sobre a Saúde Humana (TOXICAM), enfocou os parâmetros toxicológicos, como seu potencial genotóxico, pelos testes do cometa e micronúcleo em sangue periférico e medula óssea e carcinogenicidade pelos ensaios de FCA e FHA. Os dois ensaios foram divididos em 4 grupos (FCA- GI=Controle Negativo, GII=Controle Positivo/DMH III=10.000ppmLETE e GIV=50.000ppmLETE); (FHAGI= Controle Negativo, GII=Controle Positivo/DEN, GIII=10.000ppmLETE e GIV=50.000ppmLETE). Entretanto, na 3ª semana foi realizada hepatectomia parcial em todos os animais dos respectivos grupos do ensaio de FHA. No teste do cometa foram utilizados 10 animais como controle positivo (controle interno - MNU-N-metil-N-nitrosourea), e 10 animais como controle negativo nos respectivos ensaios (FCA e FHA). Os testes em questão indicaram que o LETE não promove aumento do número de criptas...
Fast oxidation of organic matter on tropical soils is another evidence of the great advantage of using biosolids as conditioners once they are able to improve biological, chemical and physical characteristics of the soil with remarkable consequences on agricultural productivity. Therefore, the present project aimed at verifying genotoxic and carcinogenic potential plots of sludge from sewage treatment plants in a pre-defined watershed region at Piracicaba, Capivari and Jundiaí (PCJ1). These data may provide support to evaluate risks on human populations and the environment exposed to sludge from sewage treatment plants. In the study, 140 Wistar male rats, 8 weekold, were used. They were exposed, via chow, to a 10.000 and 50.000 ppm concentration of sludge from sewage treatment plants during 6 to 8 weeks with DEN initiators (diethylnitrosamine) and DMH (1,2-dimethylhydrazine) as mentioned in protocols (Figures 4 and 5). Toxicological evaluation of LETE developed by Center of Evaluation of Environmental Impact on Human Health (TOXICAM) focused toxicological parameters with its genotoxic potential by comet and micronucleus assays on peripheral blood and bone marrow in Wistar rats and carcinogenicity using ACF and AHF assays. Both assays were divided into 4 groups (ACF- GI=Negative Control, GII=Positive Control/DMH III=10.000ppmLETE and GIV=50.000ppmLETE); (AHF-GI=Negative Control, GII=Positive Positive/DEN, GIII=10.000ppmLETE and GIV=50.000ppmLETE). Therefore, on the 3rd week partial hepatectomy was performed in every animal from AHF assays respective groups. assays and to FCA comet test, using MNU (N-methyl-N-nitrosourea) as positive control. The tests in question indicated that the SS not promote increased number of aberrant crypts in the colon, number and area of foci of altered hepatocytes in the liver, lesions in DNA (comet), and also, significantly increased the frequency of micronucleus in...