Binding of the antitumor compound cisplatin to DNA locally distorts the double helix. These distortions correlate with a decrease in DNA melting temperature (Tm). However, the influence of cisplatin on DNA stability is more complex because it decreases the DNA charge density. In this way, cisplatin increases the melting temperature and partially compensates for the destabilizing influence of structural distortions. The stabilization is stronger at low Na+ ion concentration. Due to this compensation, the total decrease in the DNA melting temperature after cisplatin binding is much lower than the decrease caused by the distortions themselves, especially at low [Na+]. It is shown in this study that, besides Na+ concentration, pH also strongly influences the value of a change in the melting temperature caused by cisplatin. In alkaline medium (pH=10.5-10.8), a fall in the melting temperature caused by platination is enhanced several times with respect to neutral medium. Such a stronger drop in Tm is explained by a decrease in pK values of base pairs caused by lowering the charge density under platination that facilitates proton release. At neutral pH, the proton release is low for both control and platinated DNA and does not influence the melting behavior. Therefore, lowering in the charge density under platination, besides stabilization, gives additional destabilization just in alkaline medium. Destabilization caused by structural distortions due to this pH induced compensation of stabilizing effect is more pronounced. In the presence of carbonate ion, destabilization caused by high pH value is strengthened. As a decrease in DNA charge density, interstrand crosslinking caused by cisplatin also increases the DNA stability due to loss in the entropy of the melted state. However, computer modeling of DNA stability demonstrates that interstrand crosslinks formed by cisplatin do not stabilize long DNA. It is shown that the increase in Tm caused by interstrand crosslinking itself is compensated for by a local destabilization of the double helix at the sites of location of interstrand crosslinks formed by cisplatin.
Scientific research in the field of healthcare contributes to solving not only medical, but also economic and social issues. One of the latest trends is the growing interest in evaluating the effectiveness of research conducted. In the current study, we have hypothesized that science contributes to the reduction of the Cancer Mortality Rate (CMR) by making awareness about and bringing attention to this disease. The purpose of our investigation is to study the possible correlation between five scientometric indicators (Web of Science Documents, International Collaborations, etc.) and CMR changes for 14 countries. Furthermore, the expenditures of GDP in both science and healthcare for each of the studied countries have been considered within the framework of cancer-science relations in order to find out the possible socio-economic impact on cancer incidence. Methodologically, the study relies on the principles of scientometric management. The research data were retrieved from Web of Science and the World Health Organization for the period from 1997 to 2017. To investigate the correlation between scientific research and the CMR, we have used bibliometric data and nonparametric statistical methods (the Kruskal-Wallis test, Spearman’s correlation coefficient) as well as the Dunn test of multiple group checks and the Shapiro-Wilk test. R language, Tidyverse package R and VOSviewer were used for data processing. The research results showed that during the period in question there was an increase in the CMR in Armenia and Georgia, while in Iran and Azerbaijan it remained almost consistent. For the rest of the countries from Asia and Europe, as well as Canada and the USA, the CMR experienced a downward trend. We have found close links between scientometric data, the CMR and economic costs for Europe and the USA. At the same time, for Armenia and neighbouring countries the correlation between the CMR and GDP was weak. Moreover, GDP costs incurred in healthcare and science did not have a positive effect on the CMR in Armenia, Azerbaijan and Georgia. This indicates that scientific and socio-economic factors are highly correlated with each other and, therefore, have a positive impact on the CMR, mainly in Europe and the USA. However, the science-health relationship in Armenia is still weak and requires efforts to prevent the continued rise in CMR levels. The findings of this study can also be applied to other fields of science and help to establish close links between scientometrics and various branches of medicine.
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