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1.
Protein & Cell ; (12): 792-808, 2020.
Article in English | WPRIM | ID: wpr-880882

ABSTRACT

Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study. Here, we review the recent technological advances in this rapidly evolving field. We focus on high-throughput detection methods and biological findings for these modifications, and discuss questions to be addressed as well. We also summarize third-generation sequencing methods, which enable long-read and single-molecule sequencing of DNA and RNA modification.


Subject(s)
Animals , DNA/metabolism , DNA Methylation , Epigenesis, Genetic , Epigenomics , Humans , RNA/metabolism , Transcriptome
2.
Biol. Res ; 50: 2, 2017. graf
Article in English | LILACS | ID: biblio-838963

ABSTRACT

BACKGROUND: Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. METHODS: A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). RESULTS: The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. CONCLUSIONS: In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting reagent.


Subject(s)
Humans , Female , DNA/metabolism , Transfection , Neoplasms/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , alpha-Fetoproteins/metabolism , Cell Line , Polymerase Chain Reaction , In Situ Hybridization, Fluorescence , Hepatocytes/metabolism , Genomics , Cell Line, Tumor , Endocytosis/genetics , DNA Fragmentation , Lipids/pharmacology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neoplasms/pathology
5.
Article in Korean | WPRIM | ID: wpr-180812

ABSTRACT

BACKGROUND/AIMS: DNA double strand breaks (DSB) is one of the critical types of DNA damage. If unrepaired, DSB is accumulated in the nucleus of cells, the cells become apoptotic or transform to tumor by way of genomic instability. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. There was no report that Helicobacter pylori (H. pylori), the gastric carcinogen, induce DNA DSB in gastric epithelium in vivo. The aim of this study was to investigate whether H. pylori induce DSB in the gastric epithelial cells of chronic gastritis. METHODS: Immunohistochemical stains were performed for the DSB markers, phospho-53BP1 and gammaH2AX, in the gastric epithelium derived from 44 peptic ulcer disease patients before and after H. pylori eradication. DNA fragmentation assay was performed in the cell line to investigate the DNA damage by H. pylori infection. RESULTS: The mean expression score of gammaH2AX was significantly higher in the H. pylori infected gastric epithelium as compared to the H. pylori eradicated gastric epithelium (8.8+/-5.5 vs. 6.2+/-5.3 respectively; p=0.008). The expression score of phospho-53BP1 between before and after eradication of H. pylori was not statistically different, but tended to be higher in H. pylori infection. DNA fragmentation was developed significantly more in the cell lines after infection with H. pylori. CONCLUSIONS: DSB of DNA damage was typical feature of H. pylori infection in the gastric epithelium.


Subject(s)
Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Cell Line, Tumor , DNA/metabolism , DNA Breaks, Double-Stranded , Female , Gastric Mucosa/metabolism , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Histones/genetics , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Peptic Ulcer/genetics
6.
Article in English | IMSEAR | ID: sea-134583

ABSTRACT

Blood Samples were kept at room temperature for a period of 3-6 months at room temperature to know the amount of quantitative DeoxyriboNucleic Acid [DNA] recovery from these samples. We are able to recover good amount of DNA for about first 3-6 weeks after which the DNA is decreased drastically and after two months there hardly any chance of intact DNA recovery from these samples. It has been concluded that blood samples recovered from scene of crime after about 1-2 months is a waste. The samples must be recovered as early as possible to recover intact DNA from them. The samples must be collected within 1-2 months from scene of crime until and unless the climate is cold enough to increases decay time. This study is very useful for the investigating authorities which can make errors while collecting blood samples for DNA analysis.


Subject(s)
Blood Specimen Collection , DNA/blood , DNA/metabolism , DNA/physiology , Forensic Sciences
7.
Article in English | WPRIM | ID: wpr-44286

ABSTRACT

The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-kappaB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-kappaB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-kappaB binding activity, even though these could enhance NF-kappaB signaling in the absence of other stimuli. Moreover this suppressed NF-kappaB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-kappaB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent.


Subject(s)
Animals , Antibiotics, Antineoplastic/therapeutic use , Apoptosis , Caspases/metabolism , Cell Line , Colchicine/pharmacology , DNA/metabolism , DNA Damage , Doxorubicin/therapeutic use , Humans , Mice , Microtubules/chemistry , NF-kappa B/antagonists & inhibitors , Neoplasms/drug therapy , Nocodazole/pharmacology , Protein Binding , Signal Transduction , Tubulin Modulators/pharmacology , Vinblastine/pharmacology
8.
Indian J Biochem Biophys ; 2009 Oct; 46(5): 389-394
Article in English | IMSEAR | ID: sea-135222

ABSTRACT

The rates of oxidation of adenosine and chlorogenic acid by tert-butoxyl radicals (t-BuO-) were studied by measuring the absorbance of adenosine at 260 nm and chlorogenic acid at 328 nm spectrophotometrically. t-BuO- radicals were generated by the photolysis of tert-butyl hydroperoxide (t-BuOOH) in presence of tert-butyl alcohol to scavenge OH. radicals. The rates and the quantum yields() of oxidation of chlorogenic acid by t-BuO-radicals were determined in the absence and presence of varying concentrations of adenosine. An increase in the concentration of adenosine was found to decrease the rate of oxidation of chlorogenic acid, suggesting that adenosine and chlorogenic acid competed for t-BuO. radicals. From competition kinetics, the rate constant of chlorogenic acid reaction with t-BuO- was calculated to be 3.20 109 dm3 mol-1 s-1. The quantum yields (expt) were calculated from the experimentally determined rates of oxidation of chlorogenic acid under different experimental conditions. Assuming that chlorogenic acid acts as a scavenger of t-BuO- radicals only, the quantum yields (cal) were theoretically calculated. expt and cal values suggested that chlorogenic acid not only protected adenosine from t-BuO- radicals, but also repaired adenosine radicals, formed by the reaction of adenosine with t-BuO- radicals.


Subject(s)
Absorption , Adenosine/chemistry , Adenosine/metabolism , Alcohols/chemistry , Alcohols/metabolism , Antioxidants/chemistry , Antioxidants/pharmacology , Chlorogenic Acid/chemistry , Chlorogenic Acid/pharmacology , DNA/metabolism , Kinetics , Oxidation-Reduction , tert-Butylhydroperoxide/chemistry
9.
Indian J Biochem Biophys ; 2009 Feb; 46(1): 9-15
Article in English | IMSEAR | ID: sea-28485

ABSTRACT

Free radicals are produced in cells by cellular metabolism and by exogenous agents. These species react with biomolecules in cells and one of the important targets is DNA. This kind of damage, often referred to as oxidative DNA damage, has consequences in various organs and particularly in brain, in view of its high metabolic activity and oxygen consumption. The consequences include mutagenesis of various kinds ranging from simple oxidation of bases to large deletions through single and double strand breaks. In brain, because of its post-mitotic nature, oxidative damage to DNA is seen more often at the level of bases. A major route for repairing oxidative damage to bases is base excision repair (BER). It is increasingly becoming apparent that defects in repairing oxidative DNA damage can lead to a number of neurological disorders like Alzheimer and Parkinson. Our recent studies have clearly demonstrated that BER is highly compromised in brain cells with increasing age and this could well be one of the major causative factors for normal aging and the associated deteriorating mental conditions, including certain neurological abnormalities.


Subject(s)
Aging , Alzheimer Disease/physiopathology , Animals , Brain/physiology , Brain/physiopathology , DNA/chemistry , DNA/metabolism , DNA Damage , DNA Repair , Free Radicals/metabolism , Humans , Mutation , Nervous System Diseases/physiopathology , Neurons/physiology , Oxidative Stress
10.
Article in English | WPRIM | ID: wpr-98677

ABSTRACT

Aldosterone has been shown to stimulate renal TGF-beta1 expression. However, the mechanisms for aldosterone-induced TGF-beta1 expression have not been clearly determined in mesangial cells. We examined the role of extracellular-signal regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and activator protein- 1 (AP-1) in the aldosterone-induced TGF-beta1 expression in rat mesangial cells. TGF-beta1 protein in the conditioned medium released from rat mesangial cells was measured by sandwich ELISA, TGF-beta1 mRNA expression was analyzed by Northern blotting, AP-1 DNA binding activity was measured by EMSA and the ERK1/2, JNK activity was analyzed by western blotting. Aldosterone significantly stimulated TGF-beta1 protein production and TGF-beta1 mRNA expression in mesangial cells in a dose-dependent manner. Aldosterone significantly increased AP-1 DNA binding activity in mesangial cells. Pre-treatment of cells with AP-1 inhibitor, curcumin, blocked aldosterone-induced AP-1 DNA binding activity as well as aldosterone-induced TGF-beta1 production. Aldosterone increased phosphorylation of ERK1/2 and JNK in mesangial cells. Pre-treatment of cells with ERK1/2 inhibitor, PD98059, or JNK inhibitor, SP600125 significantly inhibited aldosterone-induced ERK1/2 and JNK activity and subsequently TGF-beta1 production, respectively. We conclude that aldosteroneinduced TGF-beta1 expression in mesangial cells is regulated by the ERK1/ 2, JNK and AP-1 intracellular signaling pathways.


Subject(s)
Aldosterone/pharmacology , Animals , Culture Media, Conditioned/pharmacology , DNA/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation, Enzymologic , Humans , MAP Kinase Signaling System , Mesangial Cells/metabolism , Models, Biological , Phosphorylation , Protein Binding , Rats , Transcription Factor AP-1/metabolism , Transforming Growth Factor beta1/biosynthesis
11.
Indian J Exp Biol ; 2008 May; 46(5): 267-72
Article in English | IMSEAR | ID: sea-56461

ABSTRACT

On May 11, 2008 the German biophysicist Professor Fritz-Albert Popp will celebrate his 70th birthday. This is a welcome occasion to pay tribute to the scientific achievements and human qualities of a scientist whose merits as one of the founders of biophotonics and as a pioneer of quantum biophysics increasingly find appreciation internationally.


Subject(s)
Biology/history , Biophysics/history , DNA/metabolism , Germany , History, 20th Century , History, 21st Century , Humans , Photons , Quantum Theory
12.
Article in English | IMSEAR | ID: sea-16721

ABSTRACT

BACKGROUND & OBJECTIVE: Streptococcus pneumoniae is common in ocular and systemic infections and is a part of normal nasopharyngeal flora. Very few studies regarding genetic analysis of S. pneumoniae isolates causing eye infections are available. This study was undertaken to do pulse field gel electrophoresis (PFGE) analysis and ribotyping of S. pneumoniae isolates obtained from eye infections, systemic infections and nasopharyngeal flora. METHODS: Sixty one well characterized S. pneumoniae isolates (38 from ophthalmic infections, 9 from systemic infections and 14 commensals) were characterized using PFGE of the whole genome after SmaI, restriction enzyme digestion and conventional ribotyping using Escherichia coli rRNA operon as the probe. Phylogenetic tree was drawn using unweighted pair group method analysis (UPGMA). RESULTS: The 38 S. pneumoniae isolates from eye infections belonging to 15 serotypes were placed in to 11 PFGE types and 15 ribotypes. The 9 systemic isolates (7 seotypes) were distributed in 7 PFGE types and 6 ribotypes. The 14 commensal isolates were placed in 11 serotypes, 5 PFGE types and 6 ribotypes. Most of the PFGE types and ribotypes consisting of ocular isolates also contained systemic and commensal isolates. INTERPRETATION & CONCLUSION: Considerable genetic similarity was observed between the isolates from ocular and systemic infections and those colonized in nasopharynx. PFGE analysis could differentiate majority of the isolates according to site of infections. There was a considerable DNA polymorphism within the studied bacterial population.


Subject(s)
Bacterial Typing Techniques , DNA/metabolism , DNA, Bacterial/metabolism , Electrophoresis, Gel, Pulsed-Field , Eye Infections/microbiology , Genes, Bacterial , Humans , Models, Genetic , Molecular Weight , Phylogeny , Pneumococcal Infections/microbiology , Polymorphism, Genetic , Ribotyping/methods , Software , Streptococcus pneumoniae/metabolism
13.
Yonsei Medical Journal ; : 255-258, 2006.
Article in English | WPRIM | ID: wpr-51470

ABSTRACT

Familial benign hypocalciuric hypercalcemia (FBHH) is an autosomal dominant trait with high penetrance, clinically manifestating a relatively benign, lifelong, persistent hypercalcemia and hypocalciuria without hypercalcemic related complications. The calcium-sensing receptor (CaSR) plays an important role in the regulation of PTH secretion and calcium metabolism. Here we present a family with FBHH of an autosomal dominant inheritance. A heterozygous mutation of E297K (GAG -> AAG, exon 4) of CaSR gene was found in 3 family members. To our knowledge, it is the first confirmed case of FBHH with CaSR gene mutation in Korea.


Subject(s)
Sequence Analysis, DNA , Receptors, Calcium-Sensing/genetics , Pedigree , Parathyroid Hormone/analogs & derivatives , Mutation , Metabolism, Inborn Errors/genetics , Male , Korea , Hypercalcemia/genetics , Humans , Heterozygote , Genes, Dominant , Female , Family Health , Exons , DNA Restriction Enzymes/metabolism , DNA/metabolism , Adult
14.
Article in English | WPRIM | ID: wpr-47121

ABSTRACT

Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABA(A) receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABA(A) receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene and alcoholism. The GG genotype of the GABA(A) alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABA(A) beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABA(A) alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.


Subject(s)
Sequence Analysis, DNA , Receptors, GABA-A/genetics , Polymorphism, Genetic , Models, Statistical , Middle Aged , Male , Korea , Humans , Genetic Predisposition to Disease , DNA/metabolism , Chromosomes, Human, Pair 5 , Alcoholism/genetics , Age of Onset , Adult
15.
Indian J Exp Biol ; 2005 Nov; 43(11): 963-74
Article in English | IMSEAR | ID: sea-59485

ABSTRACT

Numerous factors influence male fertility. Among these factors is oxidative stress (OS), which has elicited an enormous interest in researchers in recent period. Reactive oxygen species (ROS) are continuously produced by various metabolic and physiologic processes. OS occurs when the delicate balance between the production of ROS and the inherent antioxidant capacity of the organism is distorted. Spermatozoa are particularly sensitive to ROS as their plasma membrane contains polyunsaturated fatty acids (PUFA), which oxidizes easily. They also lack cytoplasm to generate a robust preventive and repair mechanism against ROS. The transition metal ions that are found in the body have a catalytic effect in the generation of ROS. Lifestyle behaviours such as smoking and alcohol use and environmental pollution further enhance the generation of ROS and thus, cause destructive effects on various cellular organelles like mitochondria, sperm DNA etc. This article analyzes the detrimental effects of OS on male fertility, measurement of OS and effective ways to decrease or eliminate them completely. We have also provided information on oxidative stress in other systems of the body, which may be applied to future research in the field of reproductive biology.


Subject(s)
Animals , Antioxidants/chemistry , Cytochromes c/metabolism , DNA/metabolism , Fatty Acids, Unsaturated/metabolism , Fertility , Humans , Indicators and Reagents/pharmacology , Infertility, Male/pathology , Lipid Peroxidation , Male , Models, Chemical , Nitroblue Tetrazolium/pharmacology , Oxidative Stress , Reactive Oxygen Species , Semen/metabolism , Smoking , Spermatozoa/metabolism , Thiobarbituric Acid Reactive Substances/chemistry
16.
Indian J Exp Biol ; 2005 Sep; 43(9): 817-23
Article in English | IMSEAR | ID: sea-58809

ABSTRACT

Sixty-seven isolates of Phytophthora infestans collected from Himalayan hill regions and subtropical planes of India were characterized by RAPD markers to assess diversity and differentiation based on location of origin. Ten random decamer primers generated 161 polymorphic fragments. Association of P. infestans isolates on the dendrogram and PCO plot revealed two clear grouping based on geographical location of origin-hill isolates and plane isolates. Quantification of diversity by Shannon index of diversity analysis demonstrated that most of the diversity was present with a particular population (hill or plane) of P. infestans isolates, with 85% variation being within and 15% being between hill and plane isolates. Subtropical plane isolates of P. infestans exhibited higher variability compared to hill isolates and they were more dispersed on the PCO plot. No clear differentiation of isolates based on mating type was reflected on the dendrogram and PCO plot.


Subject(s)
DNA/metabolism , DNA Primers/chemistry , Genetic Markers , Genetic Variation , Models, Statistical , Phylogeny , Phytophthora/genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Random Amplified Polymorphic DNA Technique
17.
Indian J Exp Biol ; 2005 Aug; 43(8): 686-92
Article in English | IMSEAR | ID: sea-58415

ABSTRACT

Earlier studies have shown that 2-deoxy-D-glucose (2-DG), a glucose analogue and inhibitor of glycolytic ATP production selectively enhances radiation-induced damage in cancer cells by inhibiting the energy (ATP) dependent postirradiation DNA and cellular repair processes. A reduction in radiation induced cytogenetic damage has been reported in normal cells viz., peripheral blood lymphocytes and bone marrow cells. Since induction of apoptosis plays a major role in determining the radiosensitivity of some most sensitive normal cells including splenocytes and thymocytes, we investigated the effects of 2-DG on radiation induced apo tosis in these cells in vitro. Thymocytes and splenocytes isolated from normal Swiss albino mouse were irradiated with Co60 gamma-rays and analyzed for apoptosis at various post-irradiation times. 2-DG added at the time of irradiation was present till the termination of cultures. A time dependent, spontaneous apoptosis was evident in both the cell systems, with nearly 40% of the cells undergoing apoptosis at 12 hr of incubation. The dose response of radiation-induced apoptosis was essentially similar in both the cell systems and was dependent on the incubation time. More than 70% of the splenocytes and 60% of the thymocytes were apoptotic by 12 hr following an absorbed dose of 2 Gy. Presence of 2-DG marginally reduced the fraction of splenocytes undergoing apoptosis at all absorbed doses, while no change was observed in thymocytes. Presence of 2-DG did not significantly alter either the level or the rate of induction of spontaneous apoptosis in both these cell systems. These results are consistent with the earlier findings on radiation-induced cytogenetic damage in human PBL in vitro and mouse bone marrow cells and lend further support to the proposition that 2-DG does not enhance radiation damage in normal cells, while radiosensitizing the tumors and hence is an ideal adjuvant in the radiotherapy of tumors.


Subject(s)
Animals , Antimetabolites/pharmacology , Apoptosis/drug effects , Cells, Cultured , DNA/metabolism , Deoxyglucose/pharmacology , Dose-Response Relationship, Radiation , Female , Gamma Rays , Mice , Spleen/cytology , Thymus Gland/cytology
18.
Indian J Exp Biol ; 2005 Aug; 43(8): 715-21
Article in English | IMSEAR | ID: sea-55814

ABSTRACT

The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.


Subject(s)
Administration, Oral , Animals , Anti-Ulcer Agents/administration & dosage , Catalase/metabolism , Cell Proliferation/drug effects , DNA/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Free Radicals/metabolism , Gastric Mucosa/drug effects , Lipid Peroxidation/drug effects , Male , Ocimum/chemistry , Plant Extracts/administration & dosage , Plant Leaves/chemistry , Rats , Rats, Inbred Strains , Superoxide Dismutase/metabolism , Ulcer/drug therapy
19.
Indian J Exp Biol ; 2005 Apr; 43(4): 313-23
Article in English | IMSEAR | ID: sea-58336

ABSTRACT

DNA ligand Hoechst-33342 significantly enhances UV induced cytotoxicity in human glioma cell lines (BMG-1 & U-87) with supra additive increase in cell death, cytogenetic damage, cell cycle delay, apoptosis and inhibition of PLDR. Cytotoxicity of Hoechst-33342 arises due to its interference in the breakage-rejoining reaction of DNA topoisomerases by stabilization of cleavable complexes. Since topoisomerases have also been implicated in the generation of potentially lethal DNA breaks by interaction with various types of DNA damage including UV induced DNA lesions, we investigated in present studies the role of functional topoisomerases in the synergistic cytotoxicity of Hoechst-33342 and UV in a human glioma cell line (BMG-1). Topoisomerase I activity analyzed by the plasmid relaxation assay, was significantly enhanced upon UV irradiation, implying a possible role of this enzyme in the processing of UV induced lesions. However, this increase in the activity was reduced by >50% in cells incubated with Hoechst-33342 for 1 hr prior to irradiation. Imunoflowcytometric analysis of the chromatin bound topoisomerases I and II levels (cleavable complex) using topoisomerases I and II anti-antibodies showed a good correlation between the induction of apoptosis by Hoechst-33342 and UV and enhancement in the level of topoisomerase II mediated cleavable complexes. Induction of apoptosis was associated with a decline in the level of Bcl2. Taken together, these studies show that supra additive cytotoxic effects of UV-C and Hoechst-33342 in BMG-1 cells are consequences of enhanced stabilization of topo II mediated cleavable complexes and alterations in specific signal transduction pathways of apoptosis, besides the inhibition of topoisomerase mediated repair processes.


Subject(s)
Apoptosis/drug effects , Benzimidazoles/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , DNA/metabolism , DNA Damage , DNA Repair , DNA Topoisomerases/metabolism , DNA Topoisomerases, Type I/metabolism , DNA Topoisomerases, Type II/metabolism , Glioma/pathology , Humans , Ligands , Radiation-Sensitizing Agents/pharmacology , Ultraviolet Rays
20.
Indian J Exp Biol ; 2005 Mar; 43(3): 254-8
Article in English | IMSEAR | ID: sea-62327

ABSTRACT

Influence of finger millet and kodo millet on rat dermal wound healing was assessed by making a 4 cm2 (2 x 2 cm) excision wound on the shaven back of rats under ether anesthesia. Finger millet or kodo millet flour (300 mg) as aqueous paste was applied topically once daily for 16 days. The granulation tissue formed on day 4, 8 and 12 was used to estimate some biochemical parameters like protein, DNA, collagen and lipid peroxides. There was significant increase in protein and collagen contents and decrease in lipid peroxides. Biophysical parameters like rate of contraction and number of days for epithelialization were also studied. Rate of contraction was 88-90% in kodo millet and finger millet treated rats in comparison to 75% in untreated rats. The number of days for complete closure of wounds was lower for finger millet (13 days) and kodo millet (14 days) treated rats in comparison to untreated (16 days) rats. The results implicate a possible therapeutical role for finger millet and kodo millet in accelerating the process of wound healing.


Subject(s)
Animals , Collagen/metabolism , DNA/metabolism , Eleusine/metabolism , Epithelium/drug effects , Flour , Lipid Peroxidation , Male , Paspalum/metabolism , Rats , Rats, Wistar , Skin/drug effects , Time Factors , Wound Healing
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