PDF) Enhanced replicative bypass of platinum-DNA adducts in pic. Mamenta Facebook, Twitter & MySpace on PeekYou pic. Andy Macdonald: Skateboarding 

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20 Mar 2018 Evaluating the potency of environmental chemicals and drugs, to be enzymatically bioactivated to intermediates generating covalent DNA

Carboplatin inhibits DNA synthesis by binding to DNA and interfering with repair mechanism. At 8 h after administration of carboplatin, the relative occurrence of the bifunctional adducts Pt-GG (34%), Pt-AG (27%), and G-Pt-G (32%), was similar in all tissues. The same held for the monoadducts that amounted to about 7% of the total DNA platination. By contrast, DNA adducts of the clinically ineffective trans isomer of cisplatin, trans-diamminedichloroplatinum(II), are not recognized by hUBF. DNase I inhibition patterns of hUBF bound to a 100-base-pair DNA fragment containing a centrally located cis-[Pt(NH3)2](2+)-d(GpG) crosslink reveal specific protein-DNA interactions in a 14-base-pair region flanking the adduct.

Dna adducts cisplatin

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DNA-cisplatin adducts are specifically recognized by several proteins. They can be divided into two classes. 2019-01-18 · Cisplatin interacts with DNA mainly in the form of Pt-d (GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. Although cisplatin shows a broad spectrum of anticancer Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor) Proc Natl Acad Sci U S A . 1994 Jun 7;91(12):5672-6. doi: 10.1073/pnas.91.12.5672.

Its anticancer activity results from the modification of DNA through covalent cross-linkings or platinum (Pt)-DNA adducts. This book presents topical research in 

At 8 h after administration of carboplatin, the relative occurrence of the bifunctional adducts Pt-GG (34%), Pt-AG (27%), and G-Pt-G (32%), was similar in all tissues. The same held for the monoadducts that amounted to about 7% of the total DNA platination. By contrast, DNA adducts of the clinically ineffective trans isomer of cisplatin, trans-diamminedichloroplatinum(II), are not recognized by hUBF. DNase I inhibition patterns of hUBF bound to a 100-base-pair DNA fragment containing a centrally located cis-[Pt(NH3)2](2+)-d(GpG) crosslink reveal specific protein-DNA interactions in a 14-base-pair region flanking the adduct.

Dna adducts cisplatin

Radiosensitization of DNA by Cisplatin Adducts Results from an Increase in the Rate Constant for the Reaction with Hydrated Electrons and Formation of PtI. The Journal of Physical Chemistry B 2015, 119 (30) , 9496-9500.

C/ jplatin was  rate of removal oftotal platinum-DNA adducts (22). In addition, these cell lines show an increase in their removal of cisplatin ICLs3 from specific genomic regions  Binding of MutS to cisplatin adducts is thought to result in a continuous, futile cycle of repair on the opposing DNA strand, ultimately leading to cell death. Loss.

It is now accepted that spe-cific recognition of DNA–cisplatin adducts by nuclear proteins, especially from the HMG-domain family, inhibits Cisplatin, a DNA-crosslinking agent, is able to suppress DNA synthesis by conforming DNA adducts in cancer cells. Cisplatin , CAS 15663-27-1 Pack Size At high enzyme concentrations (2.5–25-fold excess over primer-template), pol β did not differentiate between cisplatin and oxaliplatin adducts for any DNA substrate tested (data not shown); therefore data are presented for cisplatin-damaged templates only. Fig. 3 shows the enzyme concentration-dependence and time course for translesion synthesis past cisplatin-GG adducts using all four DNA Then, ICP-MS was used to quantify the formation of intracellular platinum (Pt)–DNA adducts, which is thought to be crucial to the antitumor potency of cisplatin. A marked increase in Pt-DNA adducts was detected in cells after treatment with GOx/TPZ@Lipo-Pt for 7 hours ( Fig. 4H ) ( 38 ). include enhanced DNA repair (16—20),alteration in the types of platinum-DNA adducts formed (21, 22), and damage tolerance, which could result from an inability to undergo programmed cell death (23-25). In order to more fully elucidate the multiple mechanisms respon sible for cisplatin resistance, we have established a series of cisplatin DNA containing cisplatin–DNA adducts compared to control, undamaged duplex DNA. The decreased rates of translocation resulted in a decrease in the association of the p460 catalytic subunit of DNA-PK As in the case of DNA interstrand cross‐links of cisplatin, formation of interstrand cross‐links in double‐helical DNA by Pt‐DIST complexes may require distortion in this biomacromolecule resulting in duplex unwinding, interstrand cross‐links of cisplatin unwind duplex by 70–87°[[37-40]] while unwinding induced by other types of cisplatin adducts is markedly less extensive [[34-36]]. Carboplatin is a DNA synthesis inhibitor.
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Dna adducts cisplatin

accumulation were prominent features of the cisplatin-DNA adduct profile. Functional DNA repair capacity has been studied in eight human leukocyte cell lines  18 Jan 2019 Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. C) d(G-G)interstrand cisplatin crosslinks.

pilot of whole-abdominal irradiation versus doxorubicin and cisplatin che- DNA В is a stark way to assess the effects of DNA adducts on the  Peptider, oligopeptider, polypeptider, proteiner · Nukleinsyror, DNA, RNA för studier av platina-metallomet i maligna celler exponerade för cisplatin. Advances  of DNA В termed oligodeoxynucleotides В that con- tain specific DNA adducts cisplatin, whereas other toxicities were commensurate in both treatment arms.
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EGCG förändrade inte cisplatininducerad apoptos av humant härledda ( b ) Cisplatin kills cancer cells primarily by forming platinum–DNA adducts, which 

Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP. Cisplatin-DNA adducts, DNA repair, human lung carcinoma cell lines, metallothionein content Search for Similar Articles You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search. Using an antiserum originally raised against cisplatin-treated DNA, we were also able to detect platinum-DNA adducts induced by lobaplatin and oxaliplatin. Maximal nuclear staining for all three compounds was observed after a 4 h post-incubation period.


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Binding of MutS to cisplatin adducts is thought to result in a continuous, futile cycle of repair on the opposing DNA strand, ultimately leading to cell death. Loss.

When a DNA sample was dialysed against 0.1 M NH 4 HCO 3 (16 h, 37°C) immediately after cisplatin treatment, in order to block mono- to bifunctional adduct conversion, adduct levels were found similar to those after the 4–6 h post-incubation.