Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
1.
Kaohsiung J Med Sci ; 27(9): 360-70, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21914522

ABSTRACT

Chronic arsenic toxicity (arsenicosis) as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 µg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been found to be associated with increased occurrence of arsenic-induced keratosis. Of the various genes involved in the regulation of arsenic metabolism, single-nucleotide polymorphisms of purine nucleoside phosphorylase, in one study, showed increased occurrence of arsenicosis.


Subject(s)
Arsenic/toxicity , Chronic Disease/epidemiology , Arsenic Poisoning/epidemiology , Groundwater/chemistry , Humans , India , Liver Diseases/epidemiology , Lung Diseases/chemically induced , Lung Diseases/epidemiology , Skin Diseases/chemically induced , Skin Diseases/epidemiology , Water Pollutants, Chemical/toxicity
2.
Am J Med Genet A ; 146A(15): 1980-5, 2008 Aug 01.
Article in English | MEDLINE | ID: mdl-18627041

ABSTRACT

The FRAXA locus is flanked by three polymorphic STR markers DXS548, FRAXAC1, and FRAXAC2. Allele frequencies of these markers were determined on a population representing the eastern part of India comprising of 69 normal controls and 69 unrelated subjects with mental retardation, among whom 21 were fragile X patients. These frequencies were compared with published data on other Indian population and the major populations of the world. The allele and haplotype distribution of the studied population were significantly different in some respects from the major populations of the world. The increase of heterozygosities in fragile X samples (DXS548 67.5%, FRAXAC1 63.5%, FRAXAC2 68.5%) relative to the controls (DXS548 63.3%, FRAXAC1 51.0%, FRAXAC2 67.2%) suggests a multimodal distribution of fragile X associated alleles. Haplotype analyses with DXS548 and FRAXAC1 markers revealed that haplotype distribution in the normal controls and fragile X groups were significantly different, suggesting a weak founder effect.


Subject(s)
Chromosomes, Human, X , Fragile X Syndrome/genetics , Genetic Markers , Haplotypes , DNA/genetics , Female , Founder Effect , Fragile X Syndrome/epidemiology , Gene Frequency , Humans , India/epidemiology , Intellectual Disability/genetics , Male , Polymorphism, Genetic
3.
J Clin Pathol ; 59(10): 1102-3, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17021137

ABSTRACT

This report describes two patients with chronic myeloid leukaemia (CML): one of them developed accelerated phase CML and died 8 years after diagnosis and the other is at the chronic phase. Sequence analysis of reverse transcription-polymerase chain reaction products showed the presence of BCR-ABL fusion transcript e19a2. This finding suggests that CML carrying mu-BCR breakpoint may exhibit a clinical course similar to typical CML.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Adult , Disease Progression , Fatal Outcome , Humans , Male , Reverse Transcriptase Polymerase Chain Reaction/methods , Transcription, Genetic
4.
Eur J Cancer Prev ; 14(3): 281-4, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15901999

ABSTRACT

Polymorphisms associated with genes coding for glutathione S-transferase enzymes are known to influence metabolism of different carcinogens and have been associated with incidence of various types of cancer. We have determined the GST M1 and GST T1 'null' genotype frequency in 81 patients with chronic myeloid leukaemia (CML) and 123 racially and geographically matched control individuals by multiplex polymerase chain reaction (PCR). GST M1 null genotype frequencies in CML and controls were 28.4% and 27.7%, respectively. GST T1 null genotype frequencies in CML and controls were 19.8% and 7.3%, respectively. The GST T1 null genotype frequency in CML patients is significantly different from that in controls (odds ratio (OR) 3.12, 95% confidence interval (CI) 1.3-7.45, P=0.008).


Subject(s)
Glutathione Transferase/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Genotype , Humans , Male , Middle Aged , Odds Ratio
5.
Toxicol Lett ; 125(1-3): 19-28, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11701219

ABSTRACT

Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 microg/ml within 4 h, as detected by propidium iodide staining and DNA fragmentation analysis. Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of G(1) population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications.


Subject(s)
Apoptosis/drug effects , Chlorpromazine/pharmacology , Trifluoperazine/pharmacology , Animals , Calcium/metabolism , Cell Cycle/drug effects , Cells, Cultured , Cricetinae , Cricetulus , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/analysis , Tumor Suppressor Protein p53/analysis
6.
Ann Clin Biochem ; 38(Pt 3): 264-71, 2001 May.
Article in English | MEDLINE | ID: mdl-11392502

ABSTRACT

Fragile-X-linked mental retardation usually results from amplification of the CGG repeat in the 5' untranslated region of the FMR1 gene. To assess the extent of variation of the CGG repeat in the population from the eastern region of India we studied 98 mentally retarded individuals living in and around Calcutta and identified 21 distinct alleles ranging in size from 8 to 44 CGG repeats. A repeat size of 28 was the most frequent; this value is different from the most frequent repeat size found in other studies, indicating a racial or ethnic variation. Patients with the clinical features of the syndrome have been found to carry expanded CGG repeats. Thus, it can be inferred that the expansion of CGG repeats may be a frequent cause of the syndrome in our population.


Subject(s)
Fragile X Syndrome/genetics , Adolescent , Adult , Alleles , Blotting, Southern , Child , CpG Islands , DNA Methylation , Female , Humans , India , Male , Middle Aged , Mosaicism , Mutation , Pedigree , Polymerase Chain Reaction , Trinucleotide Repeats
8.
Clin Exp Med ; 1(3): 155-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11833853

ABSTRACT

Sixty-four thalassemia and E-beta thalassemia patients were studied for factors that modulate the severity of the disease; i.e., mutation of beta-globin gene, presence of alpha-deletion, and presence of an XmnI site at the -158 position of the Gy gene. Presence of alpha-deletion and/or homozygosity for the XmnI site was in general associated with less-severe disease. About 12% of the patients harbored single alpha-gene deletion, and the gene frequency of the XmnI polymophism in these patients is 0.48.


Subject(s)
Deoxyribonucleases, Type II Site-Specific , Globins/genetics , Mutation , Polymorphism, Genetic , alpha-Thalassemia/genetics , beta-Thalassemia/genetics , Disease Progression , Genetic Markers , Humans , India , Restriction Mapping , alpha-Thalassemia/physiopathology , beta-Thalassemia/physiopathology
9.
Oral Oncol ; 36(1): 76-80, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10889924

ABSTRACT

Oral tumor specimens (n = 50) from eastern Indian population were studied for the presence of mutations in the H-, K- and N-ras genes using selective oligodeoxynucleotide hybridization and restriction fragment length polymorphism analysis of polymerase chain reaction-amplified products. Mutations in H- and K-ras genes were observed at a frequency of 28 and 33%, respectively, whereas no N-ras mutation was noticed.


Subject(s)
Genes, ras/genetics , Mouth Neoplasms/genetics , Mutation/genetics , Female , Humans , India , Male , Polymorphism, Restriction Fragment Length
10.
Hum Hered ; 49(4): 232-5, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10436386

ABSTRACT

324 alleles of the beta-globin gene from unrelated thalassaemia patients native to the eastern region of India (mainly from the state of West Bengal) were analysed for beta-globin gene mutations by the amplification refractory mutation system (ARMS). The major mutations that were detected are IVS-1 pos 5 (G-C), codon 26 (G-A) and codon 30 (G-C) with frequencies of 0.45, 0.33 and 0.05, respectively. Haplotype analysis revealed a very strong linkage disequilibrium of IVS-1 pos 5 (G-C) with one particular haplotype. HbE was found to be associated with two major haplotypes. Codon 30 (G-C) was associated with a haplotype that is the same as that found in the African population. Haplotype associated with codon 8/9 (+G) was the same as that found in northwest India. These findings have implications for the use of molecular diagnosis for genetic counselling and prenatal diagnosis of beta-thalassaemia in this region.


Subject(s)
Globins/genetics , Haplotypes/genetics , Mutation , beta-Thalassemia/genetics , DNA Mutational Analysis , Humans , India , Polymorphism, Restriction Fragment Length
11.
Cancer Lett ; 125(1-2): 31-4, 1998 Mar 13.
Article in English | MEDLINE | ID: mdl-9566692

ABSTRACT

During the amplification of a 202 base pair (bp) fragment around the 61st codon of the N-ras gene, an extra band of about 150 bp in length was observed when genomic DNA from a human epidermoid carcinoma cell line was used as template. This fragment was cloned and sequenced. However, this sequence was not found in the databank. RT-PCR experiments indicated that the sequence is expressed in the cells about 8 h after serum induction. The relevant RNA hybridized to one strand of the sequence but not to the other.


Subject(s)
Carcinoma, Squamous Cell/genetics , DNA, Neoplasm/analysis , Base Sequence , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Tumor Cells, Cultured
12.
Mutat Res ; 321(3): 159-64, 1994 May.
Article in English | MEDLINE | ID: mdl-7513066

ABSTRACT

Human epidermoid carcinoma cells (Hep-2) were X-irradiated in the presence of 5-10 micrograms/ml of chlorpromazine (CPZ). Survival of the cells decreased with increasing CPZ concentration. Lymphocytes from three normal volunteers exposed to X-irradiation in the presence of CPZ showed an increased frequency of dicentric and ring formation.


Subject(s)
Cell Survival/drug effects , Cell Survival/radiation effects , Chlorpromazine/toxicity , Chromosome Aberrations , Radiation Tolerance/drug effects , Adult , Humans , Karyotyping , Lymphocytes/drug effects , Lymphocytes/radiation effects , Tumor Cells, Cultured , X-Rays
13.
Ann Genet ; 34(3-4): 270-8, 1991.
Article in English | MEDLINE | ID: mdl-1809237

ABSTRACT

Since nonrandom chromosome changes in neoplastic cells have proven to be good indicators of the site of gene alterations related to transformation, the authors examined the chromosomes of T-cell lymphomas induced in RF/J strain mice with methylnitrosourea (MNU). All treated mice developed thymic lymphomas within 10 weeks of injection. Chromosomes of the thymus cells were examined at intervals before and during lymphoma development, as well as after they were passaged in syngeneic and in nude mice for periods up to 424 days. In preparations made directly from the thymus cells nonrandom numerical and structural alterations were found that involved the X, 3, 15, 4, 8, 12, 14 and 17. (Chromosomes showing alterations are listed in decreasing order of the frequency of their occurrence). In cells passaged in nude mice the chromosomes similarly altered were the 10, X, 3, 12, 6, 1, 4, 19, 15, 18 and 14. In tumor cells passaged in syngeneic mice most of the same chromosomes were involved but the order was 15, 14, X, 1, 5, 6, 3, 11 and 12. The X, 15, 14, 3 and 12 were aberrant in both direct preparations and in those from passaged cells, suggesting that these chromosomes carry genes which, when altered, are particularly important in the multistep process of neoplastic transformation. Most of these chromosomes, or their homologs in other species, have been found to be involved frequently in several different cancers of mice and men, as for example the region on the mouse 15 carrying the Myc and Pvt-1 genes.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Chromosome Aberrations/chemically induced , Lymphoma, T-Cell/genetics , Animals , Chromosome Disorders , Female , Karyotyping , Lymphoma, T-Cell/chemically induced , Methylnitrosourea , Mice , Mice, Inbred Strains , Mice, Nude , Thymus Gland/cytology , Thymus Gland/drug effects
14.
Proc Natl Acad Sci U S A ; 85(9): 3193-7, 1988 May.
Article in English | MEDLINE | ID: mdl-2834735

ABSTRACT

The first constant region of the Tcrb gene was completely deleted from the DNA of 8/10 mouse cell lines established from 3-methylcholanthrene-induced RF/J thymic lymphomas, but 6/7 primary lymphomas contained the first constant region sequences. DNA from RF/J thymic lymphomas induced by N-methyl-N-nitrosourea was then examined serially as the tumors were passaged in vivo and adapted to growth in culture as uncloned and, in some cases, cloned lines. Patterns of Tcrb-specific restriction fragments from most tumors changed extensively during continued propagation. Analysis of the patterns often suggested that initial DNA rearrangements within the Tcrb complexes of monoclonal tumors had been followed by further rearrangements within the same genes. However, these different patterns may alternatively have represented successive outgrowth of separate lineages from lymphomas that were polyclonal in origin.


Subject(s)
Lymphoma/chemically induced , Receptors, Antigen, T-Cell/genetics , Animals , Chromosome Deletion , DNA/analysis , DNA Restriction Enzymes/metabolism , Deoxyribonuclease HindIII , Female , Lymphoma/genetics , Methylcholanthrene , Methylnitrosourea , Mice , T-Lymphocytes
15.
Mol Cell Biol ; 4(10): 2227-30, 1984 Oct.
Article in English | MEDLINE | ID: mdl-6095049

ABSTRACT

When a shuttle vector containing a tyrosine suppressor tRNA (supF) gene as a target for mutagenesis replicated in a monkey kidney cell line, the frequency of SupF+ mutations was 2.3 +/- 0.5 x 10(-3). When the host cells were treated with ethyl methanesulfonate 40 h before transfection, a 10-fold increase in SupF+ mutation frequency was observed. These results supported the hypothesis that a damage-inducible mutagenic pathway exists in mammalian cells and also demonstrated the utility of this shuttle vector for the study of mutagenesis in mammalian cells.


Subject(s)
Escherichia coli/genetics , Genetic Vectors , Mutation , Animals , Cell Line , Chlorocebus aethiops , Ethyl Methanesulfonate/pharmacology , Plasmids , Time Factors , Transfection
16.
Mol Gen Genet ; 178(3): 617-23, 1980.
Article in English | MEDLINE | ID: mdl-6248734

ABSTRACT

Recombination frequencies for two sets of genetic markers of herpes simplex virus were determined in various host cells with and without ultraviolet irradiation of the virus. UV irradiation increased the recombination frequency in all the cell types studied in direct proportion to the unrepaired lethal damage. In human skin fibroblasts derived from a patient with xeroderma pigmentosum (XP) of complementation group A, a given dose of UV stimulated recombination more than that in fibroblasts from normal individuals. On the other hand, UV stimulation of HSV recombination was slightly less than normal in fibroblasts derived from a patient with a variant form XP and from an ataxia telangiectasia patient. Caffeine, an agent known to inhibit repair of UV damage, reduced recombination in most of the cell types studied and did not suppress the UV-induced increase in recombination. These findings suggest that for virus DNA with the same number of unrepaired UV-lesions, each of the tested cell types promoted HSV-recombination to an equivalent extent.


Subject(s)
DNA, Viral/radiation effects , Gene Frequency , Recombination, Genetic , Simplexvirus/genetics , DNA Repair , Dose-Response Relationship, Radiation , Simplexvirus/radiation effects , Ultraviolet Rays
17.
Proc Natl Acad Sci U S A ; 75(5): 2378-81, 1978 May.
Article in English | MEDLINE | ID: mdl-209462

ABSTRACT

The survival of UV-irradiated herpes simplex virus on UV-irradiated Vero cells was increased over that on unirradiated cells. A time period between irradiation of the host cells and infection with virus was needed to achieve maximum reactivation. In parallel experiments in which the frequencies of occurrence of the forward mutation in the thymidine kinase gene of the virus were measured, growth of herpes simplex virus on UV-irradiated cells yielded progeny virus that had higher frequencies of TK- mutants than did progeny from infections of control cells. The time course of development of this mutagenic effect was the same as that for the development of the UV-reactivation capacity. Furthermore, development of the UV reactivation could be blocked by inhibition of protein synthesis. These results suggest that an "error prone" inducible UV-reactivation phenomenon exists in mammalian cells.


Subject(s)
Mutation , Simplexvirus/radiation effects , Ultraviolet Rays , Cell Line , Cycloheximide/pharmacology , DNA Repair , Genes, Viral , Mutation/drug effects , Mutation/radiation effects , Protein Biosynthesis , Simplexvirus/genetics , Thymidine Kinase/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...