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 kind of DNA damage does cisplatin cause?
Cisplatin delivers its attack by entering cancer cells and binding to and damaging DNA, which can lead to cell death. Cells respond to DNA damage by triggering DNA repair mechanisms that involve a number of proteins.
What causes cisplatin resistance?
Inside the tumor cell, decreased drug import, increased drug export, increased drug inactivation by detoxification enzymes, increased DNA damage repair, and inactivated cell death signaling are major mechanisms leading to cisplatin resistance.
What happens when the DNA repair enzymes locate the DNA cisplatin adducts?
Cisplatin-induced intrastrand adducts are bulky lesions that interfere with DNA replication machinery by arresting replicative DNA polymerases. The prolonged stalling of replication forks can result in the formation of DNA DSBs, and such deleterious damage can lead to gross DNA rearrangements or cell death 60.
How does cisplatin slow down DNA synthesis?
Cisplatin prevents DNA replication in cancer cells by a ligand replacement reaction with DNA in which a bond is formed between platinum and a nitrogen atom on guanine.
Can DNA adducts be repaired?
Tolerance and Repair of Lipid Peroxide DNA Adducts Although this type of lesion can be repaired by NER [106,249], such a repair is not very efficient. An alternative pathway to deal with this lesion is a replicative bypass by specialized DNA polymerase through the process of translesion DNA synthesis (TLS).
What cancers are treated with cisplatin?
Cisplatin, a chemotherapy drug, is best known for curing testicular cancer. It is also used in the treatment of a wide range of other cancers, including lung, bladder, cervical, and ovarian cancers. Cisplatin and other similar platinum-based drugs were developed with National Cancer Institute (NCI) support.
How does cisplatin slow down rate of DNA synthesis?
What are the contraindications of cisplatin?
Who should not take CISPLATIN?
- a bad infection.
- acute leukemia.
- low amount of magnesium in the blood.
- low amount of calcium in the blood.
- low amount of sodium in the blood.
- low amount of potassium in the blood.
- hemolytic uremic syndrome, a condition that affects the kidney and the blood.
- anemia.
Does cisplatin cause double strand breaks?
Cisplatin treatment results in persistent DNA DSBs and has no effect on the repair of IR-induced DNA single-strand breaks (20).
What repair mechanism would remove the bulky DNA adducts or lesions generated by cisplatin?
Nucleotide excision repair is the only known mechanism by which bulky adducts, including those generated by platinum chemotherapeutic agents, are removed from DNA in human cells.
How does cisplatin bind to DNA a level?
How is cisplatin used to repair the human genome?
The single-stranded gap in the genome is filled in by DNA polymerases and ligated, resulting in error-free repair. Although cisplatin is effective in the treatment of the indicated types of cancers, in some of the cases, drug resistance is observed.
What is the molecular weight of cisplatin platinum?
Molecular Weight(MW): 300.05. Cisplatin is an inorganic platinum complex, which is able to inhibit DNA synthesis by conforming DNA adducts in tumor cells.
How does the interaction of cisplatin with DNA cause apoptosis?
Cisplatin induces cytotoxic by interaction with DNA to form DNA adducts which activate several signal transduction pathways, including Erk, p53, p73, and MAPK, which culminates in the activation of apoptosis.
Who was involved in the discovery of cisplatin?
Cisplatin and other similar platinum -based drugs were developed with National Cancer Institute (NCI) support. They are prescribed for an estimated 10 to 20 percent of all cancer patients. In the experiment that led to the discovery of cisplatin in 1965, Barnett Rosenberg, Ph.D., was following a hunch.