Cellular senescence limits translational readthrough.

The origin and evolution of cancer cells is considered to be mainly fueled by DNA mutations. Although translation errors could also expand the cellular proteome, their role in cancer biology remains poorly understood. Tumor suppressors called caretakers block cancer initiation and progression by preventing DNA mutations and/or stimulating DNA repair. If translational errors contribute to tumorigenesis, then caretaker genes should prevent such errors in normal cells in response to oncogenic stimuli. Here, we show that the process of cellular senescence induced by oncogenes, tumor suppressors or chemotherapeutic drugs is associated with a reduction in translational readthrough (TR) measured using reporters containing termination codons withing the context of both normal translation termination or programmed TR. Senescence reduced both basal TR and TR stimulated by aminoglycosides. Mechanistically, the reduction of TR during senescence is controlled by the RB tumor suppressor pathway. Cells that escape from cellular senescence either induced by oncogenes or chemotherapy have an increased TR. Also, breast cancer cells that escape from therapy-induced senescence express high levels of AGO1x, a TR isoform of AGO1 linked to breast cancer progression. We propose that senescence and the RB pathway reduce TR limiting proteome diversity and the expression of TR proteins required for cancer cell proliferation.

Implementing Electric Potential Difference as a New Practical Parameter for Rapid and Specific Measurement of Minimum Inhibitory Concentration of Antibiotics.

New methods to determine antimicrobial susceptibility of bacterial pathogens especially the minimum inhibitory concentration (MIC) of antibiotics have great importance in pharmaceutical industry and treatment procedures. In the present study, the MIC of several antibiotics was determined against some pathogenic bacteria using macrodilution test. In order to accelerate and increase the efficiency of culture-based method to determine antimicrobial susceptibility, the possible relationship between the changes in some physico-chemical parameters including conductivity, electrical potential difference (EPD), pH and total number of test strains was investigated during the logarithmic phase of bacterial growth in presence of antibiotics. The correlation between changes in these physico-chemical parameters and growth of bacteria was statistically evaluated using linear and non-linear regression models. Finally, the calculated MIC values in new proposed method were compared with the MIC derived from macrodilution test. The results represent significant association between the changes in EPD and pH values and growth of the tested bacteria during the exponential phase of bacterial growth. It has been assumed that the proliferation of bacteria can cause the significant changes in EPD values. The MIC values in both conventional and new method were consistent to each other. In conclusion, cost and time effective antimicrobial susceptibility test can be developed based on monitoring the changes in EPD values. The new proposed strategy also can be used in high throughput screening of biocompounds for their antimicrobial activity in a relatively shorter time (6-8 h) in comparison with the conventional methods.