Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mutant cell line DRP 36, hypersensitive to nondimer DNA damage induced by exposure of cells to the Mylar-filtered solar ultraviolet (UV) radiation produced by a fluorescent sunlamp plus photoreactivating light (PRL) was isolated from the haploid ICR 2A frog cell line. The DO for mutant cells exposed to this solar UV source was 3.3 kJ/m2 compared with a DO of 7.3 kJ/m2 for the parental ICR 2A cells. In contrast, DRP 36 and ICR 2A cells exhibited similar levels of survival following 254-nm irradiation which causes the induction primarily of pyrimidine dimers. The cross-sensitivity to additional DNA damaging agents was examined, and it was determined that the DRP 36 cells are also hypersensitive to treatment with gamma-rays, ethyl methane sulfonate (EMS), cis-dichlorodiammine platinum (II) (DDP), and 4-nitroquinoline oxide (4-NQO) while exhibiting normal sensitivity to L-phenylalanine mustard (L-PAM), 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and mitomycin C (MMC).
Somat Cell Mol Genet 1985 Jul
PMID:Isolation of a mutant cell line derived from ICR 2A frog cells hypersensitive to the induction of non-dimer DNA damage by solar ultraviolet radiation. 386 Sep 65

The antisera specific for dehistonized HeLa cell chromatin were obtained by injecting rabbits or goats. Treatment of chromatin with cis-DDP crosslinked the active proteins to DNA thus preventing dissociation of the proteins in a high salt environment. Immunochemical staining of electrophoretically separated chromosomal proteins transferred to nitrocellulose sheets revealed that cis-DDP among others crosslinked the protein with m.w. of about 81 000. This protein is the only major protein antigen presented in several human tumors and absent in normal human tissues.
Mol Biol Rep 1985 Apr
PMID:Crosslinking of chromosomal antigen common in human tumors to DNA by cis-diamminedichloroplatinum (II). 404 Oct 6

The effects of the organometallic cytostatic agents titanocene dichloride (TDC) and vanadocene dichloride (VDC) and of the inorganic cytostatic drug cis-diamminedichloroplatinum(II) (DDP) on the morphologic appearance of human embryonal fibroblasts cultivated as monolayers in vitro were analyzed by light and electron microscopy. All three substances induced similar structural changes which consisted of nuclear as well as cytoplasmic alterations. Many fibroblasts enlarged but the nuclear volume increased more extensively than that of the cytoplasm. The nuclear envelopes underwent invagination so that segmented nuclei were formed and the nucleoli increased in size and density. Within the cytoplasm there was evidence of conspicuous protein synthesis, characterized morphologically by an increase in the size and number of mitochondria, Golgi apparatuses and of cisternae of the rER. The phenomena observed are interpreted as indicating unbalanced cell growth characterized by a selective inhibition of DNA synthesis, coupled with progressive RNA and protein syntheses.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Cytologic observations on the effects of metallocene dichlorides on human fibroblasts cultivated in vitro. 615 Dec 91

Cisplatin [cis-dichlorodiamine platinum (II)], a potent anti-tumor compound, stimulates immune responses by activating monocyte-macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event that mediates cellular responses, we examined whether cisplatin alters tyrosine phosphorylation in macrophages. We found that cisplatin increased tyrosine phosphorylation of several proteins in peritoneal macrophages and in P388D1 and IC-21 macrophage cell lines. Treatment of macrophages with tyrosine kinase inhibitors, genestein and lavendustin A, inhibited cisplatin-stimulated protein tyrosine phosphorylation in macrophages. Macrophages treated with cisplatin also exhibit increased fluorescence with anti-phosphotyrosine-FITC antibody. These data indicate that protein tyrosine phosphorylation plays a role in cisplatin-induced activation of macrophages.
Biochem Mol Biol Int 1995 Mar
PMID:Cisplatin stimulates protein tyrosine phosphorylation in macrophages. 753 62

The cytokine interleukin-1 alpha (IL-1 alpha) showed a cytostatic effect on human ovarian carcinoma cells and significantly enhanced the antiproliferative activity of cis-diamminedichloroplatinum(II) (cisplatin) toward the NIH:OVCAR-3 tumor cell line in culture. The factor of sensitization was 15-20-fold. The maximum levels of sensitization were observed both with simultaneous exposure to cisplatin and IL-1 alpha and with 24-hr pretreatment with IL-1 alpha. Synergy between these agents was diminished when cells were pretreated with an IL-1 alpha-specific receptor antagonist, indicating that synergistic interaction was receptor mediated. Using atomic absorption spectroscopy, we evaluated the cellular accumulation of cisplatin and the DNA platination; the results showed that IL-1 alpha increased cellular accumulation of cisplatin and DNA platination. Cisplatin did not affect IL-1 alpha accumulation in NIH:OVCAR-3 cells. Further studies showed that IL-1 alpha reduced the removal of platinum from DNA. These results strongly suggest that IL-1 alpha inhibits DNA repair, and this decrease in DNA repair may explain, in part, the strong synergistic interaction between IL-1 alpha and cisplatin in NIH:OVCAR-3 cells.
Mol Pharmacol 1995 Jun
PMID:Effects of interleukin-1 alpha on DNA repair in human ovarian carcinoma (NIH:OVCAR-3) cells: implications in the mechanism of sensitization of cis-diamminedichloroplatinum(II). 760 68

DNA interaction with cis-diaminodichloroplatinum (cis-DDP in solutions of different ionic strength was studied by flow birefringence, viscometry, circular dichroism. Though cis-DDP is not an electrolyte, electrostatic interactions are important for binding of cis-DDP with DNA probably for transporting cis-DDP to a macromolecule. The charges aqua-complex is formed by cis-DDP. The complexation being dependent on the platinum/DNA ratio in solution. Along with the increase of platinum concentration, it forms first the complexes with phosphate groups, then with bases without destruction of the DNA secondary structure. The next type of complex formation is accompanied by the local destruction of the hydrogen bonds and stacking interactions. And when the Pt/DNA ratio grows high enough, DNA is denatured. It is suggested that the stability of the complex is provided by nitrogen groups of the bases incorporated in the platinum first coordination sphere. The phosphate DNA groups play the role of counterions in the external coordination sphere.
Mol Biol (Mosk)
PMID:[Study of the interaction of a DNA molecule with coordination compounds of divalent platinum. I. Effect of cis-diaminodichloroplatinum on molecular parameters of DNA in solution]. 778 39

The objective of this study was to assess the therapeutic advantage of glutathione ester along with cisplatin. Comparisons were made with renal reduced glutathione, enzymatic antioxidants, and lipid peroxidation levels. Cisplatin caused differential toxic effects on renal antioxidants and lipid peroxidation. However administration of glutathione ester modulates the toxic effects of cisplatin observed in renal antioxidants and lipid peroxidation. The finding that glutathione ester co-administration along with cisplatin is more effective and advantageous in protecting against the nephrotoxicity of cisplatin when it was given alone.
Mol Cell Biochem 1995 Mar 09
PMID:Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. 779 48

DNA photolyase binds to and repairs cyclobutane pyrimidine dimers induced by UV radiation. Here we demonstrate that in the yeast Saccharomyces cerevisiae, photolyase also binds to DNA damaged by the anticancer drugs cis-diamminedichloroplatinum (cis-DDP) and nitrogen mustard (HN2) and by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Surprisingly, mutations in photolyase were associated with resistance of yeast cells to cis-DDP, MNNG, 4-nitroquinoline oxide (4NQO), and HN2. Transformation of yeast photolyase mutants with the photolyase gene increased sensitivity to these agents. Thus, while the binding of photolyase to DNA damaged by UV radiation aids survival of the cell, binding to DNA damaged by other agents may interfere with cell survival, perhaps by making the lesions inaccessible to the nucleotide excision repair system.
Mol Cell Biol 1994 Dec
PMID:A novel role for DNA photolyase: binding to DNA damaged by drugs is associated with enhanced cytotoxicity in Saccharomyces cerevisiae. 796 45

cis-Diamminedichloroplatinum(II) (cis-DDP) and cis,trans,cis-ammine(cyclohexylamine)-dibutyratodichloroplatinu m(IV) (ACDDP) are anticancer drugs that bind to DNA, forming replication blocking adducts. ACDDP, probably manifests its cytotoxicity through the metabolite cis-ammine(cyclohexylamine)dichloroplatinum(II) (ACDP). The biological effects of ACDP and cis-DDP were compared by studying polymerase inhibition in vitro and mutagenesis and genotoxicity in vivo in the duplex genome of bacteriophage M13mp18 replicated in Escherichia coli. cis-DDP and ACDP adducts were equally genotoxic within the statistical error limits of the analysis. Survival of genomes platinated by either drug, increased by threefold in cells pretreated with u.v. irradiation to induce the SOS functions of the host. In the M13mp18 lacZ' gene fragment, the mutagenicity of ACDP was lower than that of cis-DDP; the difference was approximately twofold at a dose of two adducts per 370 base-pair mutational target. Mutagenesis by both compounds was SOS-dependent. The structural basis for lower mutagenicity of ACDP is proposed to be its reduced reactivity at d(ApG) sites. This effect is attributed to an orientational isomerism that precludes the formation of one of two possible DNA adducts at d(ApG) residues. The types of mutations induced for both drugs were similar, but they occurred with different distributions. Both compounds induced primarily G-->T transversions at d(GpG) sites whereas G-->A transitions and A-->T transversions, many at d(ApG), d(GpNpG), and d(GpG) sites, were also well represented. The mapping of DNA adducts by DNA synthesis inhibition revealed excellent correlation between the location of DNA lesions and the sites of mutations. Analysis of the distribution of mutations and the distribution of potential platination sites revealed no sequence-dependent mutation hotspots; i.e. mutagenesis was random throughout the lacZ' region of the M13mp18 bacteriophage genome. These results offer insights into the molecular mechanism of mutagenicity of platinum anticancer drugs.
J Mol Biol 1994 Mar 04
PMID:Effects of DNA adduct structure and distribution on the mutagenicity and genotoxicity of two platinum anticancer drugs. 812 Aug 85

DNase I has been used as an enzymatic probe to visualize the conformational alteration induced in DNA by the binding of either the antitumor drug cis-platinum (cis-DDP) or the therapeutically inactive derivatives, trans-platinum (trans-DDP) and chlorodiethylene-triamineplatinum(II) (dien-Pt). We have constructed double-stranded oligonucleotides (52-mer) containing a single adduct either at the d(GG) site (cis-DDP intrastrand cross-link) or at the d(GC/GC) site (cis-DDP interstrand cross-link) or at the d(G/C) site (trans-DDP interstrand cross-link) or at the d(G) site (dien-Pt adduct). The platinated oligonucleotides are differently recognized by DNase I. As judged by DNase I, the distortions induced in the DNA double helix by the cis-DDP and trans-DDP interstrand cross-links spread over more base-pairs than that induced by the cis-DDP intrastrand cross-link.
J Mol Biol 1994 Mar 04
PMID:DNase I footprinting of cis- or trans-diamminedichloroplatinum(II)-modified DNA. 812 Sep 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>