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.

Cisplatin-induced DNA lesions and repair mechanisms. A) The nucleotide excision repair (NER) pathway is responsible for removing cisplatin-induced DNA adducts (such as 1,2 and 1,3 intrastrand adducts), while the mismatch repair (MMR) pathway can recognize but not repair these adducts.

Chemicals that form DNA adducts include: acetaldehyde, a significant constituent of tobacco smoke cisplatin, which binds to DNA and causes crosslinking, leading to death of the cell DMBA ( 7,12-dimethylbenz (a)anthracene) malondialdehyde, a naturally occurring product of lipid peroxidation This antibody enables the quantification of cisplatin-induced adducts on DNA. It has also been recently used for isolation of DNA fragments carrying adducts to enhance the sensitivity of subsequent PCR-based analyses and is central to ongoing studies of variation in the nature of cisplatin adducts formed in different cell lines. For nuclear genomes, cisplatin–DNA adducts are enriched within promoters and regions harboring transcription termination sites. While the density of GG dinucleotides determines the initial crosslinking of cisplatin, binding of proteins to the genome largely contributes to the accumulative pattern of cisplatin–DNA adducts. For the measurement of cisplatin-DNA adducts, dorsal root ganglia (lumbar) and lumbar enlargement of the spinal cord were removed on ice and frozen immediately in liquid N 2. In the second set of experiments male WT and XPA mice were exposed to repetitive applications of cisplatin. In vitro studies on both prokaryotic (bacterial) and eukaryotic (mammalian) cells revealed that DNA adducts of both cisplatin and trans -DDP blocked the action of DNA polymerase, an enzyme necessary for replication. In particular, 1,2-intrastrand adducts of cisplatin with DNA all stopped polymerases from doing their job.

1994 Jun 7;91(12):5672-6. doi: 10.1073/pnas.91.12.5672. Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor) D K Treiber, X Zhai, H M Jantzen, and J M Essigmann. Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139. See all. Hide.

DNA crosslinking agents exhibit a variety of DNA lesions, such as monoadducts, DNA-DNA interstrand or intrastrand crosslinks or DNA-protein crosslinks. after treatment with psoralen but also with acetaldehyde, cisplatin and mitomycin C in

To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific Transplatin, (an isomer of cisplatin that has the chlorine atoms opposite each other, rather than on the same side) also forms adducts with DNA, but mostly mono-adducts. It does not promote cross-linking which is the cause of the gene replication process.

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. From this it is clear that the high values reported earlier for bifunctional cisplatin adducts in

Search and Pharmacokinetic and pharmacodynamic studies on cisplatin in mice and men. However, the cellular accumulation, efflux, steady state content, and the formation of DNA adducts of the cisplatin [H-3]-DEP were not affected by adenosine- av O Hemmingsson · 2010 — Damage recognition protein HMG1 shields DNA from repair and is overexpressed in resistant cells (36). Apoptosis. Once cisplatin-DNA adducts are recognized av B Andersson · 2007 — Investigate if cisplatin-induced apoptosis in P31 wt and P31 res cells could be "Effects of cisplatin and amphotericin B on DNA adduct formation and toxicity in. A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Platinum compounds lead to cell death by forming DNA adducts and causing av CL Loprinzi · Citerat av 7 — Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and DNA repair and replication influence the number of mutations per adduct of that mitomycin C or cisplatin-induced DNA lesions are not incised by global… these authorities discuss the chemistry of cisplatin in aqueous solution, the DNA and how recognitions and processing of platinum-DNA adducts may be of cisplatin-induced ototoxicity include the formation of. platinum-DNA adducts, inﬂammation, and oxidative stress.

In this review, recent structures of cisplatin adducts are summarised, and the significance for the recognition of DNA structure by proteins is discussed. Two new structures of intrastrand roplatlnum(ll)-DNA adducts In the resistant line was 2.1-fold (approxi mately 2-fold less than the level ofenhanced bypass observed with dspla tin-DNA adducts). There was no evidence of enhanced bypass In the resistant line when cefls were treated with UV light or benzo(a)pyrene 7,8-dioI-9,1O-epoxide.These results indicate that the bypass DNA adducts formed by cisplatin [cis-diamminedichloroplatinum(II)] were measured in blood samples from 48 testicular cancer patients treated in four centers in Europe during four to six cycles with cisplatin infusions on five successive days (total samples, 112). Detect Cisplatin adducts using this rat monoclonal antibody, Anti-Cisplatin DNA Adducts Antibody, clone ICR4 validated for use in Dot Blot, ELISA & IHC. - Find MSDS or SDS, a COA, data sheets and more information. Note on 3D video: 3D videos on youtube are best viewed with a 3D viewing system such as a 3D TV or a stereoscopic 3D capable computer. There is an option for binding cisplatin-modified DNA (Chao et al., 1991; Nishio et al., 1994). Initially, it was sug-gested that the binding of these proteins might assist in damage recognition and thus promote repair.
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For nuclear genomes, cisplatin–DNA adducts are enriched within promoters and regions harboring transcription termination sites. While the density of GG dinucleotides determines the initial crosslinking of cisplatin, binding of proteins to the genome largely contributes to the accumulative pattern of cisplatin–DNA adducts.

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Cisplatin, one of the most widely used anticancer drugs, binds DNA and primarily forms 1,2-d (GpG) and 1,2-d (ApG) intra-strand cross-links; less frequently, 1,3-d (GpTpG) cross-links and inter-strand cross-links are formed.1 Similar to most clinical anticancer drugs targeting DNA, it is believed that the cisplatin–DNA adducts initiate a series of cellular events, such as blocking DNA replication and gene transcription, triggering diverse signalling pathways.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139. See all. Hide. 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.

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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]].