Abstract. The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. 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
carbo- platin was inferior to cisplatin when administered IP [31, 32]. DNA В is a simple technique to assess the effects of DNA adducts on
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. We present here data on DNA-adduct formation by cisplatin, lobaplatin and oxaliplatin in vitro and in A2780 cells. Materials and methods. Chemicals.
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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. av H Dahlén — Metylering av DNA är en av de mest studerade epigenetiska förändringarna och specifika mönster av hMLH1, utan kunde endast förklaras av en interaktion mellan AZA och cisplatin (Strathdee et al.
C) d(G-G)interstrand cisplatin crosslinks. D) DNA-cisplatin-protein adducts. Figure adapted from [194]. Source
2005-01-01 · Cisplatin and oxaliplatin DNA adducts cis -Diamminedichloroplatinum (II) (cisplatin) and cis -diammine-1,1-cyclobutane dicarboxylate (carboplatin) are widely used in chemotherapy, and are particularly effective in the treatment of testicular, ovarian, head, neck and non-small cell lung cancer. 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.
av M Johansson — behovet att genomföra analyser av cirkulerande DNA. Detta kommer att Standardbehandlingen är cisplatin i kombination med vinorelbin. diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to.
5-FU.
The cisplatin molecule binds with a protein on one side and the DNA molecule on the other.
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We have previously reported the extraordinarily high binding activity to cisplatin adducts by human upstream binding factor (hUBF The removal of certain DNA lesions via DNA repair pathways provides an opportunity for the cancer cell to survive. 6 Regardless of the type of DNA damage, the recognition of these cisplatin–DNA adducts by certain proteins is the first step in the induction of most downstream cellular events. The direct interaction of Pt–DNA adducts with The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques Polymerization by DNA polymerase η is blocked by cis -diamminedichloroplatinum(II) 1,3-d(GpTpG) cross-link: implications for cytotoxic effects in nucleotide excision repair-negative tumor cells Of the human DNA polymerases tested to date, both pol η and pol β bypass oxaliplatin–GG adducts with higher efficiency than cisplatin–GG adducts , , .Thus, the kinetics of translesion synthesis past oxaliplatin- and cisplatin–GG adducts has been characterized in detail for both pol η and pol β. 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).
Cisplatin-induced DNA lesions and repair mechanisms.
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not regulated by the DNA damage response pathway2014Ingår i: Cell Cycle, to cisplatin-induced cell cycle arrest2014Ingår i: Cell Cycle, ISSN 1538-4101,
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. Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts.