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Biomedical subjects

G Shanmugam

Publications and source records attributed to G Shanmugam.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytotoxic and genotoxic effects of cleistanthin B in normal and tumour cells.

Cleistanthin B, one of the toxic constituents of Cleistanthus collinus, was found to be cytotoxic to normal and tumour cells. In comparison with normal cells, tumour cells were sensitive to lower doses of toxin. The 50% growth inhibition (GI50) values for normal cell lines were from 2 x 10(-5) to 4.7 x 10(-4) M and for tumour cells the values ranged from 1.6 x 10(-6) to 4 x 10(-5) M. Short exposure (30 min) of Chinese hamster ovary (CHO) cells to cleistanthin B at 1-6 micrograms/ml resulted in extensive chromatid and isochromatid breaks and gaps. However there was no significant increase in cell death and DNA strand breaks in cells treated under the above conditions. Cleistanthin B induced micronucleus formation in cultured lymphocytes in a dose-dependent manner. CHO cells treated with high doses of cleistanthin B showed a decrease in cell viability and a concomitant increase in DNA strand-breaks. The cell death appears to be due to apoptosis since nucleosome-like ladders were observed in the treated cells when the DNA was electrophorized in agarose gels.

Animals↗
PubMed1995

Genotoxicity of the herbicide butachlor in cultured human lymphocytes.

Butachlor, a pre-emergence herbicide was investigated for its ability to induce sister chromatid exchanges (SCE) and chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Mitogen-stimulated lymphocytes were treated with three different concentrations (5, 10 and 20 micrograms/ml) of butachlor for 24, 48 and 72 h. Our results indicate a dose-dependent increase in the frequency of chromosomal aberrations at 24, 48 and 72 h of treatment with butachlor. No SCE was promoted by butachlor.

Acetanilides↗
PubMed1995

Genotoxicity of the herbicide fluchloralin on human lymphocytes in vitro: chromosomal aberration and micronucleus tests.

Cultured human lymphocytes were exposed to three different concentrations (2.5, 5.0 and 10.0 micrograms/ml) of fluchloralin for 24 and 48 h to assess chromosomal aberrations. A significant dose-dependent increase of chromatid type aberration was observed in these cells. Multiple aberrations (MA) were scored at all concentrations after 48 h treatment. To support these results we did micronucleus (MN) test using cytochalasin B to block cytokinesis. At lower concentrations (2.5 to 10.0 micrograms/ml) the frequency of MN induction was not significantly different. Higher concentrations of fluchloralin (20, 40 and 50 micrograms/ml) resulted in a significant dose dependent increase in number of micronucleated cells. This is the first report on genotoxic effects of fluchloralin in human cells.

Aniline Compounds↗
PubMed1995

Dimethyl sulphoxide alters mitogen induced production of diacylglycerol and GTP-binding to plasma membranes in mouse embryo fibroblasts.

Dimethyl sulphoxide (DMSO) is a polar solvent often used as an inducer of erythroid differentiation. In order to elucidate the mode of action of DMSO, we studied its effects on two early events in signal transduction, namely diacylglycerol (DAG) production and guanosine triphosphate (GTP) binding. Mouse embryo fibroblasts showed a bimodal profile of diacylglycerol synthesis in the presence of DMSO. Platelet derived growth factor (PDGF) mediated synthesis of diacylglycerol synthesis was inhibited by DMSO. Also DMSO down regulated serum induced GTP-binding to isolated plasma membranes of mouse embryo fibroblasts. However, the control and the ras (T24) oncogene transformed Rat-2 cells did not show any increase in GTP-binding on serum stimulation while showing a marginal decrease in GTP-binding in the presence of DMSO. DMSO may hence act by inhibiting the perpetuation of mitogenic signal transduction at an early stage.

Animals↗
PubMed1993

Retinoblastoma gene inhibits transactivation of HIV-LTR linked gene expression upon co-transfection in He La cells.

Co-transfection of HeLa cells with plasmids carrying human immunodeficiency virus (HIV) control elements along with plasmids harboring human retinoblastoma (RB) gene, results in the repression of transactivation of genes linked to HIV elements. Cells transfected with HIV LTR-linked chloramphenicol acetyl transferase (CAT) and TAT genes showed a dose-dependent decrease in CAT activity when increasing amounts of RB genes were transfected along with HIV genes. CAT mRNAs were not detected in HeLa cells transfected with HIV LTR CAT gene alone. Upon cotransfection of these cells with pTAT gene, large quantities of CAT messengers were observed. The TAT gene mediated expression of CAT gene was inhibited when cells were co-transfected with RB gene. These studies suggest that the RB gene represses HIV LTR directed CAT gene expression by interfering with the expression of HIV TAT gene.

Chloramphenicol O-Acetyltransferase↗
PubMed1991

Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence.

We have previously shown that dimethyl sulfoxide (DMSO) treatment of mouse embryo fibroblasts (MEF) at the early hours of mitogenic stimuli resulted in the inhibition of DNA and protein synthesis; delayed treatment of serum-stimulated cells with DMSO had little effect on the synthesis of these macromolecules. Here, we demonstrate the specific inhibition of expression of early growth response genes by DMSO in serum-stimulated MEF. The expression of interleukin 6, and of oncogenes c-myc and c-fos were inhibited when the cells were treated with 2% DMSO from the beginning of serum-stimulated growth but not after 3 h of mitogenic stimuli. Although the actin gene is an early serum-response gene, its expression was not affected by DMSO. The synthesis of another serum-induced protein, the plasminogen activator inhibitor-1 was blocked during concurrent and delayed (after 3 h of stimulation) treatment of serum-stimulated fibroblasts with DMSO. The expression of glyceraldehyde-3-phosphate dehydrogenase gene was not affected by DMSO. These results indicate that the expression of non-growth-related genes are either not affected or affected nonspecifically both at early and late stages of serum-induced growth of mouse embryo fibroblasts. The serum-induced expression of c-fos gene was abolished by DMSO treatment of MEF while the phorbol 12-myristate 13-acetate-induced expression of fos gene was not, indicating that the PMA signaling pathway was refractory to DMSO. Treatment of cells with medium containing 2% DMSO for 24-48 h prevents them from progression into cell cycle by preventing the expression of genes involved in G0-G1 transition of quiescent cells.

Actins↗
PubMed1990

Stimulation of protein synthesis by a 34 KD DNA-binding protein from human placenta.

A 34 KD DNA-binding protein fraction from human placenta stimulated endogenous protein synthesis in rabbit reticulocyte and wheat-germ cell-free systems. Though the synthesis of several proteins were stimulated by the 34 KD protein, a dose-dependent increase of two polypeptides of molecular weights 42,000 and 51,000 were distinctly observed in reticulocyte lysates. The synthesis of the major protein (beta-globin) was not affected by the 34 KD protein. In both hemin supplemented and unsupplemented lysates, the ability of 34 KD protein to stimulate the synthesis of high molecular weight (HMW) proteins was drastically reduced by Mg++ and not by dsRNA.

Animals↗
PubMed1989

Effect of dimethyl sulfoxide on mouse embryo fibroblasts: inhibition of plasminogen activator inhibitor deposition and interference with early events of serum-stimulated growth.

Quiescent and serum-stimulated cultures of Swiss mouse embryo fibroblasts (MEF) showed alterations in cell morphology including an enlargement in size upon treatment with 2% dimethyl sulfoxide (DMSO). Treatment of MEF and monkey kidney epithelial cells (MK2) with 2% DMSO at the early periods of serum-stimulated growth inhibited RNA, protein and DNA synthesis. DMSO treatment of cells at late stages of serum-stimulated growth (MEF after 1 hr and MK2 cells after 3 hr of stimulation) had little effect on DNA and protein synthesis although cell enlargement occurred in these cells. When the [35S]methionine labelled proteins of the control and the DMSO treated cells were analysed by high resolution polyacrylamide gel electrophoresis, no apparent difference was observed in the pattern of intracellular proteins of these cells. In contrast, the extracellular levels of two serum-induced secreted proteins of MEF (Mr 48,000 and 26,000) were dramatically reduced by DMSO treatment. The DMSO sensitive 48 kDa protein was found to be the major component of the extracellular matrix, while the 26 kDa protein was not. The 48 kDa protein was identified as plasminogen activator inhibitor (PAI-1). Densitometric quantitation showed a gradual accumulation of this protein in the matrix of serum-stimulated cells. The deposition of this protein in the matrix was inhibited by DMSO. Flow-cytometric quantitation of indirect immunofluorescence indicated higher intracellular levels of the 48 kDa protein in fetal calf serum (FCS) + DMSO treated cells, suggesting that the low level of this protein in the medium of DMSO treated cells is probably due to lack of transport of this protein from the cells into the medium.

Animals↗
PubMed1988

Human placental endonuclease cleaves Holliday junctions.

A partially purified endonuclease from human placenta cleaves cruciform structures. The placental enzyme is active both on extruded cruciform structures from negatively supercoiled covalently closed circular plasmid DNA and on synthetic X-junctions formed by reannealing short oligonucleotides. Plasmids containing natural or cloned palindromes such as pBR322 and pHD101-3 were used as substrates. The synthetic X-junction tetramer DNA formed by reannealing short oligonucleotides, was converted into dimer form by the enzyme. This is the first report of an enzyme activity involved in resolution of recombination intermediates in higher eukaryotes and second report of a cellular enzyme.

DNA↗
PubMed1988

Phosphorylation of brain specific membrane proteins of developing chick embryo.

Phosphorylation of plasma membrane proteins in various tissues of chick embryos was investigated during the development. A polypeptide of Mr 22,000 was found to be the major phosphorylated plasma membrane protein in embryonic brain; this protein was absent in embryonic muscle, liver, and gizzard tissues. Extraction of plasma membranes with Triton X-100 (1%) or Nonidet p40 (1%) or sodium deoxycholate (1%) resulted in the solubilization of most membrane proteins including the 22 KDa phosphoprotein suggesting that the 22 KDa protein is a membrane-bound protein. Maximum phosphorylation of the 22 KDa protein by [gamma-32P]ATP was observed at 0.01 mM Ca2+. Higher concentrations of Ca2+ (2.5 mM) inhibited the phosphorylation of the 22 KDa protein whereas 3.5 mM Mg2+ stimulated the phosphorylation.

Animals↗