Thus, induction of p53 by cisplatin resulted in the activation of these caspases contributing to nephrotoxicity [ ]. The survival of 30 Acinetobacter strains after UV treatment ranged over five orders of magnitude, with the Acinetobacter calcoaceticus—A.
The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for chromosomal crossover during meiosis.
ESCs are essential for the maintenance and regeneration of skin tissues [ 7 ]. This can provide a plausible mechanism by which cisplatin induces NER. The abundant intracellular thiols involved in the drug resistance are glutathione and metallothionein.
Ku80 must be in complex with Ku70 while Nbs1 interacts with Mre11 and Rad At this point, cells will respond by promptly halting cell division to prevent further DNA damage and allow the DNA repair mechanism to start. Interaction of Cisplatin with Cellular Thiols Although the major target of cisplatin is the nuclear DNA, it exhibits a high affinity towards sulfur donors such as cysteines and methionines forming stable Pt-S bonds.
In addition, we also investigated the DDC capacity in the liver of mice that were intraperitoneally injected with cisplatin at different circadian times CT. In addition, cisplatin was shown to induce nitrosylation of p53 preventing its mitochondrial translocation [ ].
Nuclear import of c-Abl was shown to be necessary for DNA damage-induced apoptosis [ ]. Thus, metallothionein isoforms play an important role in contributing towards cisplatin resistance. Although a plethora of literature exists on the role of p53 in contributing towards cisplatin cytotoxicity, p53 has also been associated with cisplatin resistance.
Since its approval by the Food and Drug administration incisplatin continues to be one of the most effective anticancer drugs used in the treatment of solid tumors.
This is an expensive process because each MGMT molecule can be used only once; that is, the reaction is stoichiometric rather than catalytic. Recently, microRNAs have also been shown to play a major role in cisplatin nephrotoxicity.
However, recent studies with cisplatin-resistant cancer cell lines seem to suggest otherwise [ 6667 ]. In either state the DNA is highly compacted and wound up around bead-like proteins called histones.
The accumulation of damage, to be specific, double-strand breaks or adducts stalling the replication forksare among known stimulation signals for a global response to DNA damage.
DNA damage checkpoint is a signal transduction pathway that blocks cell cycle progression in G1, G2 and metaphase and slows down the rate of S phase progression when DNA is damaged.
This review will focus on a series of chemotherapy-induced DNA lesions and highlight recent advances in our understanding of the DDR, the DNA repair pathways it activates and the cellular consequences of these converging pathways. CHK2 has also been implicated in apoptosis of renal cells and tissues as a result of cisplatin-induced p53 activation [ 94 ].
Senescence and apoptosis[ edit ] Senescence, an irreversible process in which the cell no longer dividesis a protective response to the shortening of the chromosome ends. Thus, DNA damage in frequently dividing cells, because it gives rise to mutations, is a prominent cause of cancer.
Interestingly these scaffolding proteins also share significant sequence similarity at their extreme C-termini, a feature essential for complex formation and DDR signaling. DNA damage response in cisplatin-induced AKI Cisplatin is one of the most effective chemotherapeutic drugs for the treatment of various types of malignant tumors, such as those of ovary, lung, head, bladder, and many others (Cepeda et al.,Siddik,Wang and Lippard, ).
The DNA damage response is transduced mainly via p53 and c-Abl. Cisplatin-induced DNA damage activates p53, leading to the induction of p21, GADD45, proapoptotic PUMA 𝛼, caspase-6, -7, and microRNAs such as miRa.
p53 also promotes cisplatin-induced apoptosis by binding and inhibiting the antiapoptotic Bcl-xL and also by degradation of. I have used low dose, UVC irradiation to induce cellular changes in addition to DNA damage. You should be careful in choosing your dose.
If you want primarily damage DNA, UVC is the best as it is. Title: Determining the response of tumour cells to UV light and cisplatin: Authors: Stubbert, Lawton James: Date: Abstract: Nucleotide excision repair (NER) recognizes and repairs sunlight-induced DNA damage as well as cisplatin induced intrastrand DNA cross-links.
UV light is both a mutagen and potent cytotoxic agent,which can trigger cell apoptosis by either accumulating DNA lesions or trigger CD95/Fas receptor and induce apoptosis directly (Rehemtulla et al., ).
Another well-characterized DNA damaging agent is cisplatin. Unlike UV light, It is usually introduced to the human body during chemotherapy. Apr 11, · A variety of environmental stresses, particularly UV light, can damage sun-exposed areas of the skin, such as the face and neck, BRCA1 plays a role in UV-induced DNA damage response.
UV-induced DNA damage produced BRCA1-positive foci as part of the damage response.Uv light and cisplatin induced dna damage response