DEFINING MINIMAL EFFECTIVE CONCENTRATIONS OF DNA-DAMAGING AGENTS VIA MICROSCOPIC OBSERVATION

Abstract

DNA-damaging agents (DDAs) are efficient chemotherapeutic drugs in combating malignant cells. The different types of these agents may, in certain concentrations, induce cell arrest and consequent cell death. Therefore, concentrations can be differentiated as cytostatic and cytotoxic. The identification of minimal effective concertation is important for clinical and research applications. The current traditional methods of defining effective drug concentrations are performed via IC50 concentrations (e.g., MTT assay) that represent the concentration of drug required to achieve “50% of its maximal efficacy”. However, this term in measuring cell viability for cancer studies can be vague. Sometimes IC50 values can represent a 50% decrease in cell number, thus assessing cell death. On the other hand, they also can represent a 50% decrease in cell division, thus, assessing the proliferation rate. Thus, the IC50 values can fail to represent the detailed characterization of concentration-dependent drug effect. Therefore, the novelty of our research is the detailed identification of minimal effective DDA concentrations by microscopic analysis. In this research, our goal was to identify effective DDA concentrations that a) significantly decrease proliferation rate and b) significantly increase cell death (or cytotoxic concentration). The results demonstrate that the effect of drugs was drug dependent, and Doxorubicin was more toxic compared to Camptothecin and Mitomycin-C. In conclusion, our research was able to identify novel data with defined cytostatic and cytotoxic concentrations.