The unique phenomenon of alternative splicing is gathering concern due to its promising therapeutic potential. The human genome sequencing project suggests approximately 20,000-25,000 genes. Among these, about 35-60% of genes generate multiple mRNAs by alternative splicing mechanism and contribute to the diversity of the proteomic world. This 'gene shortfall' has ignited considerable interest in alternative RNA splicing.This process leads to expression of a single gene responsible for the transcription of different mRNA isoforms that might have multiple biological functions. The disruption of splicing pattern can produce aberrant splice variants, which are implicated in more than 50% of genetic disorders including cancer. Altered splice sites in neoplastic cell contribute to the development, progression and/or maintenance of tumorous growth. The repertoire of tumor-specific variant represents a potential marker in pharmacogenomic diagnostic relevance. Alternative splice isoforms have been analyzed serendipitously by qualitative gene profiling with in silico gene prediction software. Computational approach in identifying exonic splicing enhancers in genomic DNA and focus on microarray technology will elucidate differential expression of alternative splice variants. The antisense oligonucleotides modulate alter native splicing and engender the production of therapeutic gene products. Oligonucleotides have the potential to silence the mutations caused by aberrant splicing. The efficacy of the antisense oligonucleotides lies in the chemical configuration, affinity and delivery strategies. Hence the therapeutic potential of antisense oligonucleotides as modulators of aberrant alternative splicing would be a major challenge to the upcoming proteomic era.
The aim of present study is to assess DNA integrity on the effect of exposure to a radio frequency (RF) signal from Code Division Multiple Access (CDMA) mobile phones. Whole blood samples from six healthy male individuals were exposed for RF signals from a CDMA mobile phone for 1 h. Alkaline comet assay was performed to assess the DNA damage. The combinative exposure effect of the RF signals and APC at two concentrations on DNA integrity was studied. DNA repair efficiency of the samples was also studied after 2 h of exposure. The RF signals and APC (0.2 microg/ml) alone or in synergism did not have any significant DNA damage as compared to sham exposed. However, univariate analysis showed that DNA damage was significantly different among combinative exposure of RF signals and APC at 0.2 microg/ml (p < 0.05) and at 2 microg/ml (p < 0.02). APC at 2 microg/ml concentration also showed significant damage levels (p < 0.05) when compared to sham exposed. DNA repair efficiency also varied in a significant way in combinative exposure sets (p < 0.05). From these results, it appears that the repair inhibitor APC enhances DNA breaks at 2 microg/ml concentration and that the damage is possibly repairable. Thus, it can be inferred that the in vitro exposure to RF signals induces reversible DNA damage in synergism with APC.
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