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

The effect of intercalating drugs (the anthracycline group of antibiotics, ethidium bromide, actinomycin D) on stepwise melting of DNA was studied by differential scanning calorimetry (DSC). The DSC DNA melting profile of plasmid pJL3-TB5 DNA (5277 base-pairs in length) consists of seven peaks, and all the intercalators caused shifting of these peaks, particularly those formed at the high temperature ranges, to the higher temperature ranges in a characteristic manner depending upon the binding strength of the drug. The analysis of the anthracycline group of antibiotics, such as aclacinomycin A, daunomycin, adriamycin and pyrarubicin, indicates that the difference in binding is due to the sugar moiety at position O-7 of the chromophore in these antibiotics. Analysis on the basis of the helix-coil transition theory suggests that the anthracycline group of antibiotics interact preferentially with the 5'-CG-3' sequences. The effect of various DNA-binding drugs other than intercalators on stepwise melting of DNA was then studied by DSC. The representative drugs examined were distamycin A, peplomycin, cis-dichlorodiamine-platinum(II) (cis-DDP or cis-Platin) and mitomycin C, which differ in their mode of interaction with DNA; namely, minor groove binding, strand cleavage and intrastrand or interstrand cross-linking. Distamycin A caused shifting of the DSC peaks at the low temperature ranges to a higher temperature range, whereas peplomycin and cis-DDP caused shifting of all the DSC peaks to form a broad peak at a lower temperature range, suggesting that the DSC DNA melting profiles are affected in a characteristic manner depending upon the interaction mode of the drug.
J Mol Biol 1990 Sep 20
PMID:Differential scanning calorimetric study of the effect of intercalators and other kinds of DNA-binding drugs on the stepwise melting of plasmid DNA. 169 88

The role of restricted cellular accumulation of cis-diamminedichloroplatinum(II) (cis-DDP) and altered repair of DNA-Pt-protein cross-links in the mechanism of L1210 murine leukemia cell resistance was examined. An immunochemical method was used to analyze the formation and removal of DNA-Pt-protein complexes in L1210 cells sensitive and resistant to cis-DDP. The accumulation of Pt into the cells and the binding of Pt to the DNA was measured by atomic absorption spectroscopy. The results demonstrated that both decreased accumulation of the drug and the rate of DNA-Pt protein cross-link removal may be important factors in L1210 cell resistance to cis-DDP.
Mol Biol Rep 1991 May
PMID:DNA-protein cross-linking in L1210 cells sensitive and resistant to cis-diamminedichloroplatinum (II). 174 77

The supF gene of the shuttle vector pZ189 was used as a target for the study of mutations induced by cis-diamminedichloroplatinum(II) (cis-DDP). Normal human repair-proficient fibroblasts and cis-DDP repair-deficient xeroderma pigmentosum (XP) cells were used as host cells to study the effect of cis-DDP on the inhibition of shuttle vector replication and mutagenesis. Transfection of cis-DDP-treated pZ189 into normal and XP cell lines resulted in a marked increase in the mutation frequency and a decrease in the replication efficiency of the vector. However, these effects were much greater for the plasmid propagated in XP cells. Atomic absorption spectroscopy showed that six to eight Pt-DNA adducts per plasmid were necessary to inhibit plasmid replication by 50% in normal cells. In contrast, only one to two Pt-DNA adducts were necessary to inhibit replication of the plasmid by 50% in XP cells. Analysis of mutation sites demonstrated that cis-DDP treatment resulted primarily in single and double mutations separated by one base and limited to a few locations within the 85-bp mature tRNA. Propagation of the cis-DDP-treated vector in either normal or XP cells led to predominantly transversion mutations at AGA, AGG, and GAG sites and a cis-DDP-associated deletion of 174 bp. Although mutations occurred at target sites for cis-DDP adduct formation, there was no correlation between sites of mutation and the most frequent sites of adduct formation.
Mol Carcinog 1991
PMID:Spectrum of cis-diamminedichloroplatinum(II)-induced mutations in a shuttle vector propagated in human cells. 191 Apr 83

It has been shown by genetic complementation analysis that a mitomycin C-sensitive mutant (V-H4) of Chinese hamster V79 cells is the first rodent equivalent of Fanconi anemia (FA) group A. The V-H4 mutant shows many typical characteristics of cells derived from FA patients. V-H4 cells exhibit increased sensitivity towards cross-linking agents as MMC (approximately 30-fold), cis-DDP (approximately 10-fold), DEB (approximately 10-fold), and PUVA (approximately 1.6-fold), but an only slightly increased sensitivity to monofunctional alkylating agents (EMS and MMS) and actinomycin D. V-H4 cells are also moderately sensitive to adriamycin (1.6-fold), and not sensitive to H2O2. The levels of chromosomal aberrations induced by MMC and cis-DDP treatment are higher (4- to 6-fold) in V-H4 cells than in the wild-type V79 cells. Genetic complementation analysis with other Chinese hamster mutants hypersensitive to MMC (irs1, irs1SF, UV20 and UV41) indicates clearly that V-H4 belongs to a different, new complementation group. This unique mutant is very stable and can serve as a vehicle to isolate the complementing FA-A gene from normal human DNA.
Somat Cell Mol Genet 1990 Nov
PMID:The Chinese hamster V79 cell mutant V-H4 is phenotypically like Fanconi anemia cells. 226 31

We have investigated the role of glutathione in determining the macromolecular binding and cytotoxicity of cisplatin (DDP) and melphalan (LPAM) in human ovarian carcinoma cells and DDP-resistant L1210 mouse leukemia cells. Glutathione reacted avidly with DDP in normal saline with a bimolecular rate constant of 16.2 M-1 hr-1. Glutathione had no effect on the rate of hydrolysis of LPAM, consistent with the SN1-like reaction mechanism of LPAM. Glutathione protected calf thymus DNA and bovine serum albumin from DDP platination and LPAM alkylation. Glutathione also protected nuclei isolated from human ovarian carcinoma cells from DDP platination. The importance of intracellular glutathione in determining the cytotoxicity of DDP and LPAM was assessed by depletion of glutathione with buthionine sulfoximine in three cell types. Exposure to 0.5 mM buthionine sulfoximine for 20-28 hr depleted glutathione to levels that were 10-20% of control levels. COLO 316 and 2008 human ovarian carcinoma cells, and ZCR9 mouse leukemia cells were all sensitized to LPAM cytotoxicity by this level of glutathione depletion. The dose modification factors, defined as the IC50 control cells/IC50 depleted cells, were: 2.6 +/- 0.5 for COLO 316 cells, 1.6 +/- 0.1 for 2008 cells, and 2.1 +/- 1.1 for ZCR9 cells. In contrast, glutathione depletion had a minimal effect on DDP cytotoxicity in these cells with dose modification factors of: 1.2 +/- 0.2 for COLO 316 cells, 0.8 +/- 0.3 for 2008 cells, and 1.1 +/- 0.1 for ZCR9 cells. The differential potentiation of DDP and LPAM cytotoxicity by glutathione depletion in these cells, despite the similar protection that glutathione affords macromolecules from drug binding, suggests that there are fundamental differences in the intracellular interaction of these electrophilic drugs with glutathione.
Mol Pharmacol 1986 Dec
PMID:Differential sensitization of human ovarian carcinoma and mouse L1210 cells to cisplatin and melphalan by glutathione depletion. 378 41

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

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

We have cloned and sequenced a cDNA clone coding for a metacyclic trypomastigote-specific surface glycoprotein with a molecular mass of 82 kDa (MTS-gp82). By immunoblotting and immunoprecipitation, antibodies against the recombinant protein recognized an 82-kDa protein of metacyclic trypomastigotes, without any detectable reaction towards amastigotes, epimastigotes or tissue culture-derived trypomastigotes. The insert of the MTS-gp82 cDNA clone strongly hybridized with a single 2.2-kb metacyclic trypomastigote mRNA, suggesting that the steady-state levels of mRNAs for MTS-gp82 are developmentally regulated. MTS-gp82 is encoded by a multigene family whose members are distributed in several chromosomes. Sequence analysis revealed 40-56% identity at amino acid level between MTS-gp82 and members of Trypanosoma cruzi gp85/sialidase family (TSA-1, Tt34c1, SA85-1.1). MTS-gp82 showed several amino acid motifs that are characteristic of gp85/sialidase family, such as the Asp box (SxDxGxTW), the subterminal (VTVxNVFLYNR) motif and the putative GPI-anchor sequence. On the basis of its structural features, the MTS-gp82 gene could be included in the T. cruzi gp85/sialidase family, but constituting a distinct group which is preferentially expressed in metacyclic trypomastigotes.
Mol Biochem Parasitol 1994 May
PMID:Cloning and characterization of a gene for the stage-specific 82-kDa surface antigen of metacyclic trypomastigotes of Trypanosoma cruzi. 793 22


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