However, chemically inducing DNA adducts or double-strand breaks in Lim1 of chicken retinal lim1 horizontal cells is not sensitive to cisplatin-induced cell 

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In order to determine the nature of the cytotoxic lesion (s) formed by the antitumour drugs cisplatin and carboplatln, a comparative study was made of bifunctional DNA-adduct formation by these drugs. The kinetics of bifunctional cisplatin adduct formation were studied with DNA in vitro and in cultured Chinese hamster ovary (CHO) cells.

They can be divided into two classes. One constitutes proteins which recognize DNA damage as an initial step of the nucleotide excision and mismatch repair pathways. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs Abstract. The platinum-based drug cisplatin is a widely used first-line therapy for several cancers.

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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. DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. 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.

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 ).

Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action. 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.

Dna adducts cisplatin

adducts and platinum-DNA adducts but reduced levels of ICL repair compared to bladder cancer cell lines. In those studies, Figure 1 - Cisplatin activation and DNA damage induction. A) The cisplatin activation process occurs by exchange of one or two of its chlorides for water molecules (monoaquated and diaquated, respectively).

Dna adducts cisplatin

One constitutes proteins which recognize DNA damage as an initial step of the nucleotide excision and mismatch repair pathways. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs Abstract.

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. Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action. Cisplatin-induced DNA lesions and repair mechanisms.
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Dna adducts cisplatin

REACH Nr. Det är en fotoaktiv substans som bildar DNA ADDUCTS i närvaro Efter fotoaktivering med UV-strålning binder den DNA via enkel och Cisplatin (Cisplatin). 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  DNA reparation kinetik kvantifieras med hjälp av strand-specifik primer of the formation of DNA-protein cross-links by antitumor cisplatin. Nucleic and quantification of DNA-protein adducts by ELISA-based RADAR assay. NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts.

the drug in its probable target position, was modified to allow quantitation with  Visar resultat 1 - 5 av 49 avhandlingar innehållade orden DNA adducts. Studies of Chemotherapeutic Drug Cisplatin : Activation and Binding to DNA. Swedish University dissertations (essays) about DNA ADDUCTS. Search and Pharmacokinetic and pharmacodynamic studies on cisplatin in mice and men.
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A major focus of this work has been DNA, the biological target of the drug, and examining the effects of cisplatin adduct formation on DNA-de- pendent cellular 

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.

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Cisplatin DNA Damage Map. We developed the method of Damage-seq based on the fact that bulky DNA adducts block high-fidelity DNA polymerases (2, 12). Here, we have applied Damage-seq to construct a human genome DNA damage map for cisplatin-induced damage. 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.

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. 1. IARC Sci Publ. 1994;(125):339-48. DNA adducts of cisplatin, transplatin and platinum-intercalating drugs. Leng M(1), Brabec V. Author information: (1)Centre de Biophysique Moléculaire, Centre Nationale de la Recherche Scientifique, Orléans, France. 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.