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Oxaliplatin Genotoxicity on Human Lymphocytes - Research Paper Example

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The aim of this paper is to study oxaliplatin genotoxicity on human lymphocytes through the use of cytogenetic techniques. This paper demonstrates that the mechanism of genotoxicity is different in the case of oxaliplatin. The predominant cytotoxicity demonstrated by oxaliplatin is genotoxicity…
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Oxaliplatin Genotoxicity on Human Lymphocytes
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Download file to see previous pages Oxaliplatin causes bulky DNA adducts. The absence of mismatch repair also indicated loss of p53 dependent apoptosis. CBMN could detect micronuclei which are indicative of DNA damage. Detection of micronuclei through CBMN indicated chromosome loss, breakage, rearrangement, nondisjunction, and apoptosis. All of these could mean specific genotoxic effects. These all are chromosomal aberrations, which may be caused by oxaliplatin. The mitotic catastrophe was a plausible mechanism of DNA toxicity caused by oxaliplatin through endocycling indicated in this experiment. This has been described as a process of mitotic failure induced by DNA damage leading to cell death. The other plausible mechanism that has been suggested is through decreased expression of the antiapoptotic protein, survivin, leading to cell death.
Apart from the formation of chromosomal aberrations, oxaliplatin adducts also prevent DNA mismatch repair. The final common pathway of such DNA damage is enhanced apoptosis. However, other mechanisms also have been recognized in these experiments, which include increased micronuclei formation, mitotic catastrophe, inhibition of survivin leading to increased rates of apoptosis, although some of them may be putative calling for further studies to be suggestive of a plausible mechanism.
Compounds of the platinum-based class of anticancer drugs such as cisplatin and carboplatin work through the formation of DNA crosslinks, which in turn result in specific cellular responses, namely, apoptosis and inhibition of transcription leading to arrest of cell replication. This is essentially the basis of antitumor activity exhibited by these agents (Almeida et al, 2005; Todd and Lippard, 2009) . Oxaliplatin, chemically described as 1R, 2R-diaminocyclohexane oxalatoplatinum (II), is a third generation platinum-based drug used for chemotherapy in many cancers. It is unique among platinum-based agents because of its tumor cell growth inhibition. ...Download file to see next pagesRead More
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