RESUMO
Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals.
Assuntos
Transformação Celular Neoplásica/efeitos da radiação , Dano ao DNA , Mucosa Bucal/efeitos da radiação , Neoplasias Bucais/etiologia , Neoplasias Induzidas por Radiação/etiologia , Radiografia Dentária/efeitos adversos , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/metabolismo , Neoplasias Induzidas por Radiação/patologiaRESUMO
Low-grade gliomas (LGG) comprise nearly 15-20 % of all central nervous system glial tumors. Several factors have been recognized as playing role in LGG malignant transformation (MT). A breakthrough analysis of a multidisciplinary group pointed that temozolomide may play a role in MT of LGGs. We analyzed the prevalence of MT in LGG patients submitted to adjuvant therapy (AT). We analyzed the medical charts of 43 patients with LGG submitted to surgery or biopsy and attending at Hospital do Servidor Público Estadual de São Paulo (São Paulo, Brazil), consecutively diagnosed from 1995 to 2013. 43 patients (24 women and 19 men) were evaluated, with mean age of 45.3 years. According to histology, 30 were astrocytomas (70 %), 12 (27 %) were oligodendrogliomas, and 1 (3 %) were mixed glioma. Mean follow-up time was 4.2 years with the standard deviation of 2.1. Twenty-eight patients did not receive adjuvant therapy and 15 received adjuvant therapy. From 43 patients with complete follow-up, 21 (48 %) experienced malignant transformation. Among such patients, nine were users of AT. Forty-eight percent of patients presented MT, being 60 % in the AT group and 42.8 % without AT. Our analysis revealed a high prevalence of MT in patients undergoing AT, higher than in patients without AT.
Assuntos
Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Quimiorradioterapia Adjuvante/efeitos adversos , Glioma/patologia , Adulto , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Transformação Celular Neoplásica/efeitos da radiação , Quimiorradioterapia Adjuvante/métodos , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Feminino , Glioma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Radioterapia/métodos , TemozolomidaRESUMO
Breast cancer is a major cause of global mortality in women. Curcumin exerts anti-proliferative, anti-migratory and apoptotic effects. The aim of this study was to evaluate gene expression involved in epithelial-mesenchymal transition (EMT). An in vitro model was developed with the MCF-10F immortalized breast epithelial cell line exposed to low radiation doses of high LET (linear energy transfer) α-particles (150 keV/µm) and cultured in the presence of 17ß-estradiol (estrogen). The following cell lines were used: i) MCF-10F, normal; ii) Alpha5, pre-tumorigenic, and iii) Tumor2 derived from Alpha5 injected into the nude mice. Our previous results have shown that Alpha5 and Tumor2 increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice in comparison to control. Results indicated that curcumin decreased expression of EMT-related genes in Tumor2 cell line when compared to its counterpart as E-cadherin, N-cadherin, ZEB2, Twist1, Slug, Axl, vimentin, STAT-3, fibronectin; and genes p53 and caveolin-1, as well as apoptotic genes caspase-3, caspase-8, and others such as cyclin D1 and NFκB. All these changes induced a decrease in migratory and invasive capabilities of such a cell line. Thus, it seems that curcumin may impinge upon apoptosis and metastatic properties of the malignant cells exerting antitumor activity in breast cancer cells transformed by low doses of α-particles and estrogen in vitro.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Curcumina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Estrogênios/toxicidade , Animais , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , CamundongosRESUMO
Human breast cancer is a major cause of global morbidity and mortality in women and it is a process that involves numerous molecular and cellular alterations attributed to environmental substances and agents such as hormones. Bisphosphonates, such as pamidronate, are potent antiresorptive drugs used to the treatment of metabolic bone disease, exerting anti-proliferative, anti-migratory and apoptotic effects. The aim of this study was to evaluate gene and protein expression involved in these processes. An in vitro model was developed with the MCF-10F immortalized breast epithelial cell line exposed to low radiation doses of high LET (linear energy transfer) α-particles (150 keV/µm) and cultured in the presence of 17ß-estradiol (estrogen). This model consisted of the following cell lines: i) MCF-10F, normal; ii) Alpha3, non-malignant; iii) Alpha5, pre-tumorigenic, and iv) Tumor2, derived from Alpha5 injected into the nude mice. Our previous results have shown that Alpha5 and Tumor2 increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice in comparison to control. Expression of the gene (RT-qPCR) and protein (western blotting, flow cyto-metry) was measured. The results indicated that pamidronate decreased invasion, migration and Rho-A, c-Ha-ras, p53, Serpin-1, Caveolin-1, Bcl-xL and NFκB gene and protein expression. Thus, it seems that pamidronate may impinge upon cellular proliferation, invasion, metastasis and apoptosis and it may exert antitumor activity in breast cancer cells transformed by low doses of α-particles and estrogen in vitro.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Transformação Celular Neoplásica/efeitos dos fármacos , Difosfonatos/farmacologia , Partículas alfa , Animais , Neoplasias da Mama/tratamento farmacológico , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/efeitos da radiação , Estradiol/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Camundongos , Pamidronato , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Cell-cell adhesion is mediated by members of the cadherin-catenin system and among them E-cadherin and ß-catenin are important adhesion molecules for epithelial cell function and preservation of tissue integrity. To investigate the importance of cell adhesion molecules in breast carcinogenesis, we developed an in vitro breast cancer model system wherein immortalized human breast epithelial cell line, MCF-10F, was malignantly transformed by exposure to low doses of high linear energy transfer (LET) α particle radiation (150 keV/µm) and subsequent growth in the presence or absence of 17ß-estradiol. This model consisted of human breast epithelial cells in different stages of transformation: i) parental cell line MCF-10F; ii) MCF-l0F continuously grown with estradiol at 10(-8) (Estrogen); iii) a non-malignant cell line (Alpha3); and iv) a malignant and tumorigenic cell line (Alpha5) and the Tumor2 cell line derived from the nude mouse xenograft of the Alpha5 cell line. Expression levels of important cell adhesion molecules such as α-catenin, ß-catenin, γ-catenin, E-cadherin and integrin were found to be higher at the protein level in the Alpha5 and Tumor2 cell lines relative to these levels in the non-tumorigenic MCF-10F, Estrogen and Alpha3 cell lines. In corroboration, cDNA expression analysis revealed elevated levels of genes involved in the cell adhesion function [E-cadherin, integrin ß6 and desmocollin3 (DSc3)] in the Alpha5 and Tumor2 cell lines relative to the levels in the MCF-10F, Estrogen and Alpha3 cell lines. Collectively, our results suggest that cell adhesion molecules are expressed at higher levels in malignantly transformed breast epithelial cells relative to levels in non-malignant cells. However, reduced levels of adhesion molecules observed in the mouse xenograft-derived Tumor 2 cell line compared to the pre-tumorigenic Alpha5 cell line suggests that the altered expression levels of adhesion molecules depend on the tumor tissue microenvironment.
Assuntos
Neoplasias da Mama/metabolismo , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/metabolismo , Neoplasias Induzidas por Radiação/metabolismo , Animais , Caderinas/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/efeitos da radiação , Desmocolinas , Feminino , Xenoenxertos , Humanos , Cadeias beta de Integrinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Radiação Ionizante , Microambiente Tumoral , alfa Catenina/metabolismo , beta Catenina/metabolismo , gama Catenina/metabolismoRESUMO
Curcumin (diferuloyl methane) is a well known antioxidant that exerts antiproliferative and apoptotic effects. Curcumin effect was evaluated in a breast cancer model that was developed using the immortalized breast epithelial cell line MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17ß-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) MCF-10F; ii) Estrogen cell line; iii) a malignant Alpha3 cell line; iv) a malignant and tumorigenic, Alpha5 cell line; and v) a cell line derived from Alpha5 injected into the nude mice that gave rise to Tumor2 cell line. Curcumin decreased anchorage-independent growh in transformed breast cancer cell lines in comparison to their counterparts and increased the percentage of cells from G0/G1 with a concomitant increase in G2/M phases, as well as a decrease in PCNA and Rho-A protein expression. Among the oncogenes, c-Ha-Ras and Ras homologous A (Rho-A) are important cell signaling factors for malignant transformation and to reach their active GTP bound state, Ras proteins must first release bound GDP mediated by a guanine nucleotide releasing factor (GRF). Then curcumin decrease RasGRF1 protein expression in malignant cell lines. Further, differential expression levels of cleaved (ADP) ribose polymerase 1 (PARP-1) and phosphorylated histone H2AX (γ-H2AX) were observed after curcumin treatment. It seems that PARP-1 similar to H2AX, confers cellular protection against radiation and estrogen-induced DNA damage mediated by curcumin. Therefore, targeting either PARP-1 or H2AX may provide an effective way of maximizing the therapeutic value of antioxidants for cancer prevention.
Assuntos
Anticarcinógenos/farmacologia , Mama/citologia , Curcumina/farmacologia , Células Epiteliais/efeitos dos fármacos , Estrogênios/farmacologia , Citoesqueleto de Actina/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos da radiação , Células Epiteliais/efeitos da radiação , Estrogênios/fisiologia , Feminino , Humanos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , ras-GRF1/metabolismoRESUMO
BACKGROUND: It is well documented that over-expression of the c-myc proto-oncogene occurs in the vast majority of mouse thymic lymphomas induced by gamma-irradiation, evidencing the importance of this gene in T-cell lymphomagenesis. However, it remains unknown whether elevated levels of c-myc expression are driven by extra c-myc copy numbers. MATERIALS AND METHODS: Here we use a quantitative test on the basis of real-time PCR to determine the cellular copy number of c-myc in a set of 14 g-radiation- induced thymic lymphomas obtained from (C57BL/6J x BALB/cJ) F1 hybrid mice with increased mRNA c-myc expression. RESULTS: Since 5 out of 14 (35.7%) cases had no extra copy numbers of c-myc, gene amplification was obviously not the cause of c-myc over-expression in these tumours. In the remaining 9 tumours, c-myc over-expression was also accompanied with extra DNA copy numbers. Therefore, c-myc amplification might be a consequence of the genomic instability subsequent to the up-regulation of c-myc. However, linear regression analysis showed a lack of correlation between increasing DNA copy numbers and mRNA over expression of c-myc in these tumours (r = 0.029, p = 0.94). CONCLUSION: De-regulation of c-myc does not necessarily imply amplification of this gene in these tumours. This report is, to our knowledge, the first one comparing c-myc amplification with expression in lymphomas of the T-cell lineage.
Assuntos
Raios gama/efeitos adversos , Dosagem de Genes , Genes myc , Linfoma/genética , Neoplasias Induzidas por Radiação/genética , Reação em Cadeia da Polimerase , Neoplasias do Timo/genética , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos da radiação , Sistemas Computacionais , Cruzamentos Genéticos , DNA de Neoplasias/genética , Amplificação de Genes , Linfoma/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias Induzidas por Radiação/etiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Neoplasias do Timo/etiologiaRESUMO
BACKGROUND/AIMS: In spite of the new technology--stapler, antibiotics, anesthesia and new surgical and diagnostic procedures--the prognosis on treatment of cancer of the rectum has not changed in the last 50 years. Survival rates of 50-55% seems immutable in all published series. The main course for those results is the high incidence of recurrence, either local or widespread. Local recurrence is directly related to the number of undifferentiated cells and to the grade of wall invasion. So any kind of treatment that would diminish the number of undifferentiated cells and the size or the tumor wall penetration certainly would decrease the local recurrence rate, lengthening the interval free from cancer and, perhaps, modifying the long-term survival rate. Between 1978-1996, a total of 287 patients with rectal adenocarcinoma were treated by pre-operative RTD. METHODOLOGY: The same RDT protocol was used in all the patients: 400 cGy, 200 cGy/day, during 4 consecutive weeks (anterior and posterior pelvic fields). Surgery was performed 7-10 days after completion of RDT. RESULTS: Statistical analysis of the whole group showed that pre-operative RDT does decrease frequency of undifferentiated cells. Moreover, the incidence of local recurrence diminished after irradiation by 3.48%. Pre-operative RDT reduces tumor volume and wall invasion, as well as the mortality rate due to local recurrence (2.43%) and alters long-term survival rate (80.17%). CONCLUSIONS: Pre-operative radiotherapy is really effective in reducing the number of undifferentiated cells and in diminishing the carcinomatous infiltration of the rectal wall.