Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antimutagênicos/farmacologia , Coronantes/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfócitos/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas de Plantas/farmacologia , Células Cultivadas , Humanos , Linfócitos/efeitos dos fármacosRESUMO
The mRNA levels of P53gene, as well as NPM1, Kras, c-Myc, p14(ARF) genes, which, according to the published data, code for the proteins regulating the p53 activity, were studied using RT-PCR method in blood cells of patients with different localization of tumor process (prostate cancer, breast cancer and head and neck cancer) before and after application of radiation therapy. Changes in gene expression of cancer patients were compared with the control group of healthy donors. We have established that all patients had a decreased level of the Kras gene expression even before radiotherapy; moreover, the group of patients with prostate cancer had a low content of mRNA in NPM1 and p14(ARF), and the group of patients with head and neck cancerhad a reliably reduced mRNA in P53, NPM1 and p14(ARF). The radiation therapy did not cause essential changes in the expression of these genes of cancer patients, ecpect for the Kras gene, whose the mRNA level in the group of patients with head and neck cancer was reliably lower than the mRNA level prior to beginning of radiation therapy. The correlations of P53, NPM1, Kras, p14(ARF) gene expression were studied. We have shown that p14(ARF) mRNA level negatively correlates with Kras mRNA (R = -0.6, p = 0.002) and P53 mRNA levels (R = -0.49, p = 0.013) in the control group of healthy donors. A positive correlation was observed between P53 mRNA and NPM1 mRNA (R = 0.54, p = 0.006). Similar correlations between mRNA levels of these genes in blood cells were absent in the cancer patients before radiotherapy. After radiotherapy in patients with prostate cancer, p14(ARF) mRNA level positively correlated with NPM1 mRNA (R = 0.7, p = 0.001) and negatively with Kras mRNA (R = - 0.5, p = 0.03). Our results provide evidence that expression P53, NPM1, Kras and p14(ARF) genes may be coordinated in blood cells of healthy donors. The low expression levels of the studied genes in patients can contribute to the increase in the mutation changes in blood cells of the examined subjects after the action of genotoxic factors.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias , Fator 1 de Ribosilação do ADP/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/genética , Neoplasias/radioterapia , Proteínas Nucleares/sangue , Nucleofosmina , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas c-myc/sangue , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53/sangue , Proteínas ras/sangueRESUMO
Codon 312 and 751 polymorphisms ofXPD gene and codon 399 polymorphism of XRCC1 gene of peripheral blood lymphocytes in patients with Down syndrome (DS) (46 individuals), Ehlers-Danlo syndrome (EDS) (47 individuals) and in a group of healthy donors (control) (40 individuals) have been studied. Frequency of XPD genotype (G312G) coding for the most effectively functioning form of XPD protein was lower in patients with DS (26%) than in a group of healthy donors (42.5%) (p = 0.035), whereas no significant differences with the control were revealed for this codon in patients with EDS. No patients with XPD genotype (C751C) (p = 0.036) were revealed in a group of EDS patients, while this genotype was found in 16% of a group of healthy donors and in 17% of patients with DS. The trend of XRCC1 genotype frequency reduction (A399A) (p = 0.085) in EDS patients (3.9%) compared with the group of healthy donors (13.5%) and DS patients (13.3%) has been obtained. These data show that polymorphisms of the excision repair genes under study are accompanied by an elevated individual radio sensitivity in patients with DS. Genes investigated (their polymorphic variants) did not participate in the mechanisms for radio sensitive phenotype formation in EDS patients.
Assuntos
Proteínas de Ligação a DNA/genética , Síndrome de Down/genética , Síndrome de Ehlers-Danlos/genética , Tolerância a Radiação/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adolescente , Criança , Pré-Escolar , Códon/genética , Reparo do DNA/genética , Frequência do Gene , Humanos , Lactente , Linfócitos/efeitos da radiação , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
The genes of detoxication, MTHFR and p53 were studied in Down' and Ehlers-Danlos syndrome cells. The frequency GSTM1(0/0) genotype in Down syndrome patients was in 1.5 times higher than in control cells (p < 0.069). Opposite the frequency GSTM1(0/0) genotype in Ehlers-Danlos syndrome was 23.3% 2 times lower than in control cells (p < 0.034). This indication was in 2 times lower in women cells than in men cells and in 3 times lower than in control cells (p < 0.026). The mutations of p53 gene (7th exon) were detected in 4 from 11 Down patients (36.7%; in 2 cases af women and men), in Ehlers-Danlos patients--in 5 cases and only in men (29.4% among all the observed patients). The observations 24 healthy donors weren't revealed any mutations (p < 0.013-0.001). The hypothesis about the connection between gene polymorphisms which take a part in genome stability and radiosensitivity in Down and Ehlers-Danlos patients was developed.
Assuntos
Síndrome de Down/genética , Síndrome de Ehlers-Danlos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Tolerância a Radiação/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Criança , Pré-Escolar , Feminino , Frequência do Gene , Humanos , Masculino , Polimorfismo GenéticoRESUMO
The frequency of mutant forms p53 and N-Ras genes was investigated in DNA from peripheral blood of the patients by method Polymerase Chain Reaction - Single Strand Conformation Polymorphism Analysis. The patients were investigated in late period after radiation accidents exhibited acute radiation syndrome. It is established that the mutations among patients in areas of codons 246-250 exon 7 of p53 gene and codon 12 of N-Ras gene were meet more often than in control group. It is shown that these mutations possibly arise in insignificant number of the cells with the radiation-induced genomic instability. Possibility of use of mutations in protooncogenes and tumour suppressor genes as markers of risk of development of the main thing from delayed effects of exposure to ionizing radiation - malignant tumours is discussed.
Assuntos
Síndrome Aguda da Radiação/genética , Genes ras/genética , Instabilidade Genômica/genética , Mutação , Neoplasias Induzidas por Radiação/genética , Proteína Supressora de Tumor p53/genética , Neoplasias da Mama Masculina/genética , Marcadores Genéticos/genética , Humanos , Neoplasias Renais/genética , Leucemia Mieloide Aguda/genética , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias Retais/genética , Fatores de Risco , Neoplasias da Glândula Tireoide/genéticaRESUMO
Cells of a diploid line obtained from embryos with the Down's syndrome, known to be unable to repair gamma-induced DNA damage, were treated with natural (garlic extract, retinol) and synthetic (crown compound) antimutagens and with adapting factors (heat shock, low CdCl2 concentrations, 10(-8) M). The protective effect was evaluated by registering DNA breaks and cell survival, and the protection coefficients were calculated. The most effective results were obtained with the use of the garlic extract and retinol. No protection of the DNA structure was observed when cells were treated with low concentrations of cadmium chloride and then with high concentrations, i. e., no adaptive response (AR) was formed under these conditions. The spectrum of proteins in treated and control cells as well as detoxication genes (GSTM1, GSTT1 , CYPIA1) were determined.
Assuntos
Antimutagênicos/farmacologia , Cloreto de Cádmio/toxicidade , Dano ao DNA/fisiologia , Reparo do DNA , Mutagênicos/toxicidade , Polimorfismo Genético , Adaptação Fisiológica , Cloreto de Cádmio/farmacologia , Linhagem Celular , Coronantes/farmacologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Síndrome de Down/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fibroblastos/efeitos da radiação , Alho/química , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Temperatura Alta , Humanos , Extratos Vegetais/farmacologia , Vitamina A/farmacologiaRESUMO
Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients. Mutations were not found in the control group. Due to the small sample size, the results of this study should be interpreted with caution and need replication in larger studies.
