RESUMO
The survey dedicated to the 70th anniversary of the Prof. N. N. Petrov Research Institute of Oncology, St. Petersburg, gives a basic idea of molecular pathogenesis of tumor in humans, particular emphasis being placed on the clinical and applied aspects of molecular oncology. The survey is intended for a wide audience including doctors, professors and undergraduate students majoring in medicine and biology.
Assuntos
DNA de Neoplasias/genética , Mutação , Neoplasias/genética , Proto-Oncogenes/genética , RNA Neoplásico/genética , Southern Blotting , Western Blotting , Terapia Genética , Humanos , Neoplasias/terapia , Reação em Cadeia da PolimeraseRESUMO
The Mendelian inheritance of population genetic markers according to their zygosity has been established in a population investigation carried out in Kazakhstan and the northwestern region of Russia, using the 5'PstEJ6.6 DNA probe genetic variability both for persons of different nationality in a population and between two distant populations has been observed. Said procedure has proved more acceptable than the M13 phage DNA test for mass screening examinations because it involves genome analysis on the basis of DNA markers common to each population.
Assuntos
Impressões Digitais de DNA/métodos , Sondas de DNA/genética , Genes ras/genética , Genética Populacional , Regiões Promotoras Genéticas/genética , Adulto , DNA/genética , Suscetibilidade a Doenças , Feminino , Genoma Humano , Genótipo , Humanos , Cazaquistão , Masculino , Federação Russa , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/genéticaRESUMO
Primary structure of 5'-end 16S RNA gene of mitochondrial DNA (mDNA) isolated from rat liver tissue within 20 hrs after treatment with 1,2-dimethyl hydrazine, was analyzed. The preparations studied did not contain mutations induced by the drug. The region of mDNA analyzed appears not to be a preferential target for mutagenic effect of 1,2-dimethyl hydrazine unber these experimental conditions.
Assuntos
Carcinógenos/toxicidade , DNA Mitocondrial/metabolismo , Dimetilidrazinas/toxicidade , Mitocôndrias Hepáticas/metabolismo , 1,2-Dimetilidrazina , Animais , Sequência de Bases , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/genética , Mitocôndrias Hepáticas/efeitos dos fármacos , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , RatosRESUMO
Expression of protooncogenes c-myc, N-myc, c-fos, Ha-ras 1, Ki-ras 2, yes, abl, src, N-ras, met and mos was studied in human gastric tumors and in rat gastric mucosal membrane during gastric carcinogenesis induced in rats by means of N-methyl-N'-nitro-N-nitroso guanidine (MNNG). Elevated expression of protooncogenes c-myc, c-fos, Ha-ras 1, Ki-ras 2, N-myc and Raf 1 was observed in carcinomas of human stomach. Amplification of Ha-ras 1 protooncogene was found in the human gastric tumor and metastasis. Point mutation was not detected in 12 the codon of Ha-ras I protooncogene. Expression of these protooncogenes was not altered during gastric carcinogenesis induced by MNNG in rats. However, within early steps of cancerogenesis (9 days, 3 months) amplification of ribosomal genes occurred in rat gastric mucosal membrane and in adenocarcinoma developed, while the tumor growth was accompanied by activation of mitochondrial genes.
Assuntos
Proto-Oncogenes , Neoplasias Gástricas/induzido quimicamente , Animais , Northern Blotting , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Amplificação de Genes , Expressão Gênica , Genes myc , Genes ras , Humanos , Masculino , Metilnitronitrosoguanidina/toxicidade , Metástase Neoplásica , Hibridização de Ácido Nucleico , Ratos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
By the restriction analysis method we established that methylation of the 5'-end cytosine in 5'-m5CC-3' duplexes had individual specific features. This genetic peculiarity did not change even in DNA from human stomach carcinomas.
Assuntos
Citosina/análogos & derivados , DNA/genética , Variação Genética , Citosina/metabolismo , DNA/metabolismo , Sondas de DNA , Genes ras , Humanos , Neoplasias Gástricas/genética , Úlcera Gástrica/genéticaRESUMO
The expression of 10 protooncogenes has been quantitatively studied in liver of male rats L10 age of 1, 10.5, 22 and 37 months. It was shown that a number of specific mRNA transcripts and, therefore, the levels of expression of protooncogenes C-MYC, C-FOS, N-MYC, HA-RAS, KI-RAS, SIS, ABL, YES, MOS and MET in rat liver were constant during life span. These data are in accordance with resistance of the rat strain L10 to spontaneous hepatocarcinogenesis.
Assuntos
Fígado/metabolismo , Proto-Oncogenes/genética , Fatores Etários , Animais , Sondas de DNA , Expressão Gênica , Neoplasias Hepáticas/genética , Masculino , Hibridização de Ácido Nucleico , RNA , RNA Mensageiro/genética , Ratos , Transcrição GênicaRESUMO
A method of the restriction analysis by Msp I enzyme has been used to analyze the 12th codon of Ha-ras-1 protooncogene in 10 human carcinomas and in the stomach mucosa adjacent to them their 5 metastases into the regional lymph nodes and in 2 ulcers. No point mutation was found.
Assuntos
Adenocarcinoma/genética , Códon/genética , Genes ras/genética , Proto-Oncogenes/genética , RNA Mensageiro/genética , Úlcera Gástrica/genética , DNA/genética , DNA de Neoplasias/genética , Humanos , Metástase Linfática , Biologia Molecular , Mutação , Proto-Oncogene MasRESUMO
The data on the changes in the isoenzyme spectrum of pepsinogen-pepsin inversely correlating with the development and retaining of the malignant condition of gastric mucosa in human and animals are reviewed. The results of the molecular-genetic studies of gastric carcinogenesis, in particular the role of protooncogenes--oncogenes in this process are presented.
Assuntos
Neoplasias Gástricas/etiologia , Animais , Fenômenos Bioquímicos , Bioquímica , Cães , Mucosa Gástrica/metabolismo , Humanos , Oncogenes , Proto-Oncogenes , Coelhos , Ratos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoAssuntos
Genes ras , Neoplasias/genética , Polimorfismo de Fragmento de Restrição , Proto-Oncogenes , Alelos , Suscetibilidade a Doenças , Feminino , Marcadores Genéticos , Genoma Humano , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Ovarianas/genética , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide/genéticaRESUMO
Ha-ras restriction fragments' length polymorphism (RFLP) in white blood cells and stomach tissues from patients with carcinoma and ulcer of the stomach was examined. Genomic DNAs were digested with Xho I, Pvu II, Pst I, Msp I, Bcn I, Mva I, Bsp RI. No Ha-ras-1 polymorphic variants specifically associated with the cancer disease were detected. RFLP of the 3'-noncoding sequence of c-Ha-ras-1 gene had got features of the definite human population. The cells forming the tissue were examined and individual peculiarity of the methylated residues disposition seemed to influence RFLP of the 5'-noncoding sequence of c-Ha-ras-1.
Assuntos
Proteínas de Membrana/genética , Úlcera Péptica/genética , Polimorfismo de Fragmento de Restrição , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Neoplasias Gástricas/genética , DNA/genética , Humanos , Hibridização de Ácido Nucleico , Proteínas Proto-Oncogênicas p21(ras)RESUMO
The study is concerned with the expression of src, sis, fos, myc, Ha-ras, Ki-ras, N-ras, mos, and abl proto-oncogenes in the brain, heart, liver, kidneys, lung, stomach, cross-striated muscle cells and in leukocytes. Some of these genes are shown to be actively transcribed in adult intact rats. Their expression depends on the tissue specificity. Most of the investigated proto-oncogenes are expressed in the liver and kidney weakly, and in the brain and heart--more strongly. A correlation is observed between fos and Ha-ras proto-oncogenes' expression in organs of intact rats.
Assuntos
Regulação da Expressão Gênica , Proto-Oncogenes , Animais , Diferenciação Celular , DNA/genética , Crescimento , Masculino , Mitose , Hibridização de Ácido Nucleico , Especificidade de Órgãos , RNA/genética , Ratos , Maturidade Sexual , Transcrição GênicaRESUMO
The expression of c-Ha-ras-1, Ki-ras, N-ras, abl, src, fos and myc protooncogenes was analyzed in 13 cases of human gastric carcinomas. The transcriptional activity of both fos and myc protooncogenes was found to be disturbed in 47% and 42% of cases, respectively. An overexpression of fos protooncogenes as well as an appearance in some cases of atypical foc-mRNA transcripts were established. Only an elevation of the number of myc mRNA copies was observed. In one patient with gastric carcinoma a c-Ha-ras-1 overexpression was detected due to its amplification both in tumour tissues and in regional metastasis. The expression of other protooncogenes under investigation was similar to those found in normal gastric mucose. In addition, no differences in expression in protooncogenes mentioned above plus sis protooncogene were established in unchanged, premalignant and malignant stomach tissues in the course of N-methyl-N'-nitro-N-nitrosoguanidin-induced carcinogenesis.
Assuntos
Carcinoma/genética , Mucosa Gástrica/efeitos dos fármacos , Regulação da Expressão Gênica , Metilnitronitrosoguanidina/toxicidade , Proto-Oncogenes , Neoplasias Gástricas/genética , Animais , Carcinoma/induzido quimicamente , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Humanos , Metástase Linfática , Masculino , Hibridização de Ácido Nucleico , Proto-Oncogene Mas , RNA Neoplásico/análise , RNA Neoplásico/genética , Ratos , Neoplasias Gástricas/induzido quimicamente , Fatores de Tempo , Transcrição GênicaRESUMO
An increased number of transcripts of c-Ha-ras, c-myc, c-sis and c-src protooncogenes has been detected in the chemically induced rat rhabdomyosarcoma related to the expression of that genes in normal muscle tissue of inbred rats. A degree of transcription elevation varies among the tested genes: c-src, c-Ha-ras and c-sis, c-myc.
Assuntos
Proto-Oncogenes , Rabdomiossarcoma/genética , Animais , Metilcolantreno , Hibridização de Ácido Nucleico , RNA Mensageiro/genética , RNA Neoplásico/genética , Ratos , Rabdomiossarcoma/induzido quimicamenteRESUMO
Both c-myc and c-Ha-ras 1 oncogenes amplification and enhanced expression were revealed in some human mammary and thyroid carcinomas by the molecular genetic analysis. Amplification proves to be a second possible molecular mechanism of the ras family protooncogene activation besides a point mutation. The coexistence of c-myc and c-Ha-ras 1 in some human primary carcinomas suggests a multistep process of carcinogenesis.
Assuntos
Neoplasias da Mama/genética , Amplificação de Genes , Proto-Oncogenes , Neoplasias da Glândula Tireoide/genética , Enzimas de Restrição do DNA , DNA de Neoplasias/genética , Humanos , Hibridização de Ácido NucleicoRESUMO
DNA samples obtained from tumors and adjacent mucosa of the large bowel of a patient with large bowel multiple neoplasia were examined after Southern. The procedure established amplification of v-myc oncogene-related DNA sequences in 1 out of 5 tumors tested. Restriction fragments of amplified myc-specific sequences and matching c-myc and N-myc loci of the human genome differed in size.
