ABSTRACT
State Research Center "GosNIIgenetika", Moscow, 117545 Russia). Association of polymorphic markers Arg72Pro of TP53 gene and T309G of MDM2 gene with risk of non small cell lung cancer has been studied in Russians of Moscow region. We found an association of minor Pro/Pro genotype of polymorphic marker Arg72Pro (OR = 5.46, p = 8 x 10(-6)) and TG genotype of polymorphic marker T309G (OR = 5.57, p = 0.007) with non small cell lung cancer development. We have also showed a strong association of both Pro/Pro and TG genotypes with development of adenocarcinoma (OR = 8.71, p = 3 x 10(-6) and OR = 8.13, p = 0.003) and squamous-cell lung cancer (OR = 4.2, p = 0.001 and OR = 7.02, p = 0.002). We have finally found highly reliable association of combined susceptible genotypes of polymorphic markers Arg72Pro and T309G of TP53 and MDM2 genes with non small cell lung cancer and both its subtypes (OR = 7.9, p = 0.01; OR = 9.12,p = 0.02; OR = 7.31, p = 0.03, respectively).
Subject(s)
Adenocarcinoma/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/genetics , Genetic Predisposition to Disease , Genotype , Lung Neoplasms/genetics , Polymorphism, Genetic , Proto-Oncogene Proteins c-mdm2/genetics , Tumor Suppressor Protein p53/genetics , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Female , Genetic Markers , Humans , Lung Neoplasms/pathology , Male , Middle AgedABSTRACT
Chronic effects of low doses of low intensity ionizing radiation (IR) on biological objects have now become of great social significance. This has given a considerable impetus to research into biological effects and mechanisms of such exposures both in Russia and abroad. This paper provides an overview of physicochemical and molecular bases of the IR influence at small doses and the ways of cell protection from the radiation damage, as well as the analysis of characteristic features and differences in the effects of radiation at small and high doses. We consider the DNA radiation damage both in cell cultures and in vivo, as well as processes and results of their repair. Particular attention is paid to the changes in the basic paradigms of radiation biological effects of small doses.
Subject(s)
DNA Damage , DNA Repair , DNA , Animals , DNA/chemistry , DNA/genetics , DNA/radiation effects , Dose-Response Relationship, Radiation , HumansABSTRACT
A new class of substances exhibiting radioprotective and radiosensitizing effects depending on the concentration of the substance has been found. The radioprotective effect is probably due to the resonant absorption of radiation energy and its transformation into low-energy forms, as well as reactions with water radiolysis products. We studied the effects of 2,5-difeniloxazole and di[2-(5-feniloxazolil)]benzene in various concentrations in conjunction with irradiation on the growth of melanoma B-16 in mice and the average time of their lives. When using individual doses of irradiation and doses of preparations, we observed an increase in the average lifetime of mice and a reduced tumor size. These data allow us to conclude about the possibility of using these substances in the radiotherapy of tumors.
Subject(s)
Benzene Derivatives/pharmacology , DNA/drug effects , Oxazoles/pharmacology , Radiation-Protective Agents/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Benzene Derivatives/chemistry , Cell Membrane/drug effects , Cell Membrane/radiation effects , DNA/radiation effects , DNA Breaks, Double-Stranded/drug effects , Dose-Response Relationship, Radiation , Melanoma, Experimental , Mice , Mice, Inbred BALB C , Oxazoles/chemistry , Radiation-Protective Agents/chemistry , Radiation-Sensitizing Agents/chemistry , Spleen/cytology , Spleen/drug effects , Spleen/radiation effects , Water/chemistry , Whole-Body IrradiationSubject(s)
DNA/genetics , DNA/radiation effects , Escherichia coli/metabolism , Neutrons , Calibration , Cytoplasm/metabolism , DNA/metabolism , DNA, Bacterial/radiation effects , Dose-Response Relationship, Radiation , Gases , Genome, Bacterial/radiation effects , Macromolecular Substances/metabolism , Polymers/chemistry , Salts/chemistry , Spectrophotometry, Infrared/methods , TemperatureABSTRACT
We examined now an ultraweak thermalized neutron field (UTNF) affects the structural transformation in DNA macromolecules at room temperature. IR-spectroscopy, electrophoresis, and filtration through nitrocellulose filter measurements revealed that UTNF irradiation with a fluence of F(n) - 1.0 - 3.7 x 10(7) n/cm2 (the absorbed dose as low as 10 - 50 microGy) can induce non negligible structural changes in DNA macromolecules in film as well as in an aqueous solution. These structural changes appear as a type of reversible conformational transition from the A-form to a disordered state, as well as through intermolecular cross-link formations and the generation of double-strand breaks.
Subject(s)
DNA Breaks, Double-Stranded/radiation effects , DNA, A-Form/chemistry , Neutrons , Animals , Cattle , Electrophoresis , Mice , Nucleic Acid Conformation/radiation effects , Spectrophotometry, InfraredABSTRACT
It is well known that AKR mice with spontaneous leucosis are more sensitive to ionizing irradiation as compared to normal F1 (CBA x C57BL) mice. A study on changes of the structural characteristics of spleen DNA and level of protein p53 in the blood serum under the action of low-level gamma-irradiation in a dose of 1.2 cGy and injections of 10(-14) or 10(-4) mol/kg phenozan was performed. The changes in the structural characteristics of DNA (the adsorption on nitrocellulose filters and number of double-strand breaks) and p53 content were observed for each line of mice under gamma-irradiation and each phenozan concentration. Both factors showed long-time post-effects, and structural changes in AKR DNA were consistent with the life span of these mice. Phenozan in the above doses has abolished the induction of double-strand breaks in case of irradiation of F1 mice in a dose of 1.2 cGy and showed long-time post-irradiation effect. These facts suggest a radioprotection property of phenozan.
Subject(s)
Antioxidants/administration & dosage , DNA/drug effects , Gamma Rays/adverse effects , Leukemia, Radiation-Induced/genetics , Leukemia, Radiation-Induced/prevention & control , Phenylpropionates/administration & dosage , Animals , DNA/radiation effects , DNA Breaks, Double-Stranded , Female , Mice , Mice, Inbred Strains , Mice, Mutant Strains , Spleen/drug effects , Spleen/radiation effects , Tumor Suppressor Protein p53/bloodABSTRACT
The effects of 2,5-diphenyloxazole ad its derivatives suggested as nontraditional radioprotectors on mice spleen DNA structure were studied. The effects of these compounds were studied on intraperitoneal injection with and without subsequent X-ray exposure of mice to a dose of 12 cGy. The formation of double-strand breaks and DNA conformation change (by adsorption on NC filters) were recorded. A genotoxic effect of 2,5-diphenyloxazole and its derivatives, a nonlinearity of their dose-response relationships and different effects depending on the substance concentration were found. Some of the compounds exhibited radioprotective properties in certain concentration.
Subject(s)
DNA/radiation effects , Mutagens/toxicity , Oxazoles/pharmacology , Radiation-Protective Agents/pharmacology , Animals , DNA/analysis , DNA/drug effects , DNA Damage , Female , Mice , Mice, Inbred BALB C , Mutagens/chemistry , Mutagens/pharmacology , Nucleic Acid Conformation/drug effects , Nucleic Acid Conformation/radiation effects , Oxazoles/chemistry , Oxazoles/toxicity , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/toxicity , Spleen/chemistry , Spleen/radiation effectsABSTRACT
Hydrogen peroxide in low concentrations have effect on DNA structural characteristics both in solution at 38 degrees C and in vivo, in mice organs.
Subject(s)
DNA Damage , DNA/drug effects , DNA/radiation effects , Hydrogen Peroxide/pharmacology , Adsorption , Animals , Cells, Cultured , Cricetinae , Cricetulus , Electrophoresis, Agar Gel , In Vitro Techniques , Mice , Radiation Dosage , Spleen/drug effects , Spleen/metabolism , Spleen/radiation effects , TemperatureABSTRACT
It was shown that thermalized neutrons in superlow doses were capable of inducing detectable structural transformations in DNA films and DNA solutions.
Subject(s)
DNA/radiation effects , Neutrons , Adsorption , Animals , Cattle , DNA/analysis , DNA Damage/radiation effects , Electrophoresis, Agar Gel , Mice , Models, Theoretical , Nucleic Acid Conformation/radiation effects , Radiation Dosage , Solutions , Spectrophotometry, Infrared , Spleen/metabolism , Spleen/radiation effects , Temperature , Thymus Gland/metabolism , Thymus Gland/radiation effects , Time FactorsABSTRACT
The dynamics of conformational changes in thymus and spleen DNA of 3-9-month old mice line AKR during the development of spontaneous lymphoid leukosis was studied by the retention on nitrocellulose filters. It was shown that the degree of DNA condensation for healthy and deceased animals differs, which is probably due to different intensity of endogenous oxidation. Seasonal conformational changes in spleen DNA from healthy mice of line F1 were revealed.
Subject(s)
DNA, Neoplasm/chemistry , Leukemia, Lymphoid/metabolism , Adsorption , Aging , Animals , Collodion , DNA, Neoplasm/metabolism , Female , Leukemia, Lymphoid/pathology , Male , Mice , Mice, Inbred AKR , Nucleic Acid Conformation , Organ Size , Oxidation-Reduction , Seasons , Spleen/chemistry , Spleen/pathology , Thymus Gland/chemistry , Thymus Gland/pathologyABSTRACT
The antioxidative activity of two plant growth promoters, ambiol and phonk, in a model system of photo-induced glycyltriptophane oxidation was measured. It was shown that ambiol has a significant antioxidative activity, whereas phonk is a weak antioxidant. The effects of these compounds on DNA conformation were studied in vitro and in vivo (on wheat seed shoots). In vitro ambiol had a stronger effect as compared with phonk, whereas in vivo the latter produced a more essential effect than ambiol. The assumption was done that both compounds affect indirectly the genome expression activity. Possible mechanisms of biological activity of each compound are discussed.
Subject(s)
Antioxidants/pharmacology , Benzimidazoles/pharmacology , Nicotinic Acids/pharmacology , Plant Growth Regulators/pharmacology , Antioxidants/chemistry , Benzimidazoles/chemistry , DNA, Plant/chemistry , Dipeptides/chemistry , Electrophoresis, Agar Gel , Germination , Luminescent Measurements , Nicotinic Acids/chemistry , Nucleic Acid Conformation , Oxidation-Reduction , Plant Growth Regulators/chemistry , Seeds/drug effects , Seeds/genetics , Triticum/drug effects , Triticum/geneticsSubject(s)
DNA Methylation , Nitric Oxide/physiology , Animals , Kinetics , Male , Oxidation-Reduction , Rats , Rats, WistarSubject(s)
4-Aminobenzoic Acid/chemistry , 4-Aminobenzoic Acid/pharmacology , DNA/chemistry , Escherichia coli Proteins , Escherichia coli/genetics , Gene Expression Regulation, Bacterial/drug effects , Oxidants/pharmacology , Trans-Activators , Bacterial Proteins/genetics , DNA/drug effects , Escherichia coli/drug effects , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Kinetics , Lipid Peroxidation , Liposomes/chemistry , Malondialdehyde/analysis , Oxidants/chemistry , Phosphatidylcholines/chemistry , Regulon/drug effects , Transcription Factors/genetics , Vitamin K/chemistry , Vitamin K/pharmacologyABSTRACT
In paper the new aspects of action regularity of ionizing radiation of low intensity on the biophysical and biochemical characteristics of bio-objects and populations are considered. From the point of view of breaking the connection between occurrence of damages and work of systems of restoration at low intensity irradiation, are described the dose dependence of different types--from threshold up to extreme and a plateau curve, differing among themselves only by a parity of these processes. The features of action of low intensity irradiation on bio-objects and populations--change of structure of a population, sensitivity to action of external stimulus, force of connections between the elements of regulatory systems--allow to consider the low intensity irradiation as the factor capable to cause unpredictable transition of quasistationary systems in new status.
Subject(s)
Dose-Response Relationship, Radiation , Models, Biological , Animals , Biopolymers/radiation effects , DNA/radiation effects , Mice , Spleen/radiation effectsABSTRACT
Analysis of literature and own experimental data as well as the up-to-date conception of heterogeneous damage of cell genome allows the author to conclude that there are some sensitive regions in DNA, which are the sites of DNA attachment to nuclear matrix. The role of conformational changes in chromatin is considered in formation of long-term consequences of low-dose irradiation of mammalian and human.
Subject(s)
DNA/radiation effects , Nucleic Acid Conformation , Animals , Carcinoma, Ehrlich Tumor/ultrastructure , Chromatin/radiation effects , Chromatin/ultrastructure , DNA/ultrastructure , DNA, Neoplasm/radiation effects , DNA, Neoplasm/ultrastructure , Dose-Response Relationship, Radiation , Humans , Liver/radiation effects , Liver/ultrastructure , Mice , Spleen/radiation effects , Spleen/ultrastructureABSTRACT
It was shown that spin trap feeding resulted in a decrease of oxidation of rat DNA. This is an evidence of free radical mechanism of endogenous DNA oxidation.
Subject(s)
Cyclic N-Oxides/chemistry , DNA/chemistry , Nitrogen Oxides/chemistry , Spin Labels , Animals , Electron Spin Resonance Spectroscopy , Mice , Mice, Inbred CBA , Oxidation-Reduction , Pyridines , RatsABSTRACT
Aging of female CBA mice was accelerated by irradiation of the head at 10 and 12 Gy. The mean life span was shortened by 10.5 and 21%, respectively. The distribution by life span was similar in the control and experimental groups. The level of DNA oxidation products in the urine was normalized within 28 days after irradiation. At the age of more than 7.5 months, the irradiated mice had a lower body weight. Age-related changes of body temperature in irradiated (10 Gy) and control mice mostly coincided; the differences were evident after 18 months. It was concluded that physiological and radiation-induced aging are significantly similar.
Subject(s)
Aging/physiology , Aging/radiation effects , Animals , Body Temperature/physiology , Body Temperature/radiation effects , Body Weight/physiology , Body Weight/radiation effects , DNA/radiation effects , Female , Guanine/analogs & derivatives , Guanine/urine , Head/radiation effects , Longevity/physiology , Longevity/radiation effects , Mice , Mice, Inbred CBA , Oxidation-ReductionABSTRACT
The level in urine of 8-hydroxy-2'-deoxyguanosine (8-oxodG) is the standard biochemical marker of endogenous oxidation of DNA in humans and animals. A new method for assay of 8-oxodG in mouse and rat urine was developed. A modified method for solid phase extraction of this substance was developed. The baseline levels of 8-oxodG and 8-oxoG was measured in control rats and the effects of various compounds added to the diet or removed from the diet were assessed. The contribution of iron and copper ions to endogenous oxidation of DNA is close to 50%. Among the tested microelements (Zn, Cr, Se), the effect of selenium was the highest and depended on the duration of the selenium-deficient diet. Carcinogens including 20-methylcholanthrene and caffeic acid and a substituted quinone significantly enhanced guanine oxidation of rat DNA.
