Discussion part - Lab Report Example

Upon administration of satraplatin, a number of metabolites (JM118, JM383, JM518, JM559 and JM149) are formed (Raynaud et al. 1996). Platinum complexes can kill tumour cells owing to their ability to form various covalent adducts on DNA (Brabec, 2002). DNA conformation is affected by the formation of adducts which also impacts some of the other intracellular processes including DNA damage recognition by specific proteins, DNA polymerisation and repair, all of which contribute to the antitumour activity of the platinum-based compounds e.g., cisplatin (Johnson et al., 1989). Most of the chemotherapeutic drugs that have been found to be clinically valuable act by damaging DNA in proliferating cells.

Thus, DNA damage is pivotal to the origin, progression and treatment of cancer. Also, higher the cytotoxicity of the compound, better the efficacy. In the present study, both the Comet assay and the MN technique were employed to assess the genotoxic effects of satraplatin and vinflunine. The comet assay essentially evaluates primary DNA damage, which is reparable, by measuring single- and/or double-strand breaks in individual cells (Collins et al., 1997). Hydrogen peroxide (H2O2) is an oxidising agent that is produced intracellularly during normal metabolism or when exposed to external agents such as solar UV radiation.

H2O2 can cause DNA damage through sugar and base modifications (Dizdaroglu, 1992). In this study, human lymphocytes incubated for 30 min with 50μM H2O2 showed substantial DNA damage, seen as a 7-fold increase in the mean Olive Tail Moment (OTM) values compared to the control sample (Fig. 1). In those cells that were subjected to a one-hour pre-incubation with satraplatin (0.02μM - 200μM) a significant reduction in OTM values was obtained. The observed decrease in OTM, ranging from 30% - 75%, was directly proportional to the concentration of satraplatin used.

The mode of action of many