What does cisplatin do to DNA?
Cisplatin binds to the N7 reactive center on purine residues and as such can cause deoxyribonucleic acid (DNA) damage in cancer cells, blocking cell division and resulting in apoptotic cell death. The 1,2-intrastrand cross-links of purine bases with cisplatin are the most notable among the changes in DNA.
What is PT DNA?
Dry films of platinum chemotherapeutic drugs covalently bound to plasmid DNA (Pt-DNA) represent a useful experimental model to investigate direct effects of radiation on DNA in close proximity to platinum chemotherapeutic agents, a situation of considerable relevance to understand the mechanisms underlying concomitant …
How do platinum anticancer drugs bind to DNA?
Each platinum drug will bind two bases either through nucleosides on the same strand (intrastrand binding) or through individual bases, on different strands (interstrand binding). The most readily formed DNA adduct is the 1,2-GpG intrastrand adduct.
Why is platinum used to treat cancer?
Platinum-based drugs are effective against cancer because at their centre is a platinum atom joined to two ammonion molecules and two chloride ions. The compound is negatively charged, but when it enters the cancer cell it becomes positively charged because the chloride ions are replaced by water molecules.
What kind of DNA damage does cisplatin cause?
The chemotherapy drug cisplatin kills cancer cells by damaging their DNA. It has been used for treating a variety of cancer types for almost four decades.
What drug is given with cisplatin?
Droperidol 1 mg was given intramuscularly (IM) 15 minutes prior to beginning cisplatin. Repetitive doses of intravenous (IV) metoclopramide, 2 mg/kg in 75 ml 5% dextrose in water over 15 minutes was given 30 minutes prior to, and at 1 1/2, 4 1/2, and 7 1/2 hours after beginning cisplatin chemotherapy.
How are DNA adducts repaired?
These include direct base repair by alkyltransferases and excision of the DNA damage by base excision repair (BER) or nucleotide excision repair (NER). Mismatch repair is involved in the detection and repair of mismatched DNA adducts.
How does damage seq work?
In Damage-seq, cisplatin-damaged DNA fragments are immunoprecipitated using an antibody specific to platinum-bound DNA prior to sequencing using a library preparation protocol dependent on the stalling of DNA polymerase by DNA adducts. …
Which drug contains platinum?
The platinum-based drugs cisplatin, carboplatin and oxaliplatin are regularly prescribed in the treatment of cancer and while they are effective, their use is limited by their severe, dose-limiting side effects (also referred to as adverse effects/events).
What causes platinum resistance?
Several mechanisms contribute to the development of drug resistance, including tumor heterogeneity, reduced drug concentration to the target, alteration in drug target structure, increased repair of the lesions induced. Depending on the drug and tumor under investigation, one or more mechanisms can take place.
Is platinum harmful to the human body?
The health effects of platinum are strongly dependent upon the kind of bonds that are shaped and the exposure level and immunity of the person that is exposed. Finally, a danger of platinum is that it can cause potentiation of the toxicity of other dangerous chemicals in the human body, such as selenium.
Is platinum toxic to humans?
Platinum toxicity has the ability to cause DNA alterations, cause cancer, allergic reactions of the skin and mucous membranes, it can cause damage to organs such as the kidneys and intestines and has been known to damage hearing ability.
How does DNA repair contribute to platinum resistance?
There are multiple factors that contribute to platinum resistance but alterations of DNA repair processes have been known for some time to be important in mediating resistance. Recently acquired knowledge has provided insight into the molecular mechanisms of DNA repair pathways and their effect on response to chemotherapy.
How to thank TFD for the existence of platin?
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What are platinum-based antineoplastic drugs used for?
Platinum-based antineoplastic. Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of chemotherapy, popular drugs include cisplatin,…
Where does platinum-based antineoplastic agent crosslink DNA?
As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause crosslinking of DNA as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of guanine, forming a 1, 2 intrastrand crosslink.