Notes
Even though a period of thorough studies in the field of cancer research durates more than a century, several crucial answers about carcinogenesis, factors that impact cancer's progression, and about the most successful way of treating cancer with the least or even without side effects have not yet been answered. Therefore, we needed no additional reasons to study cancer, with an entirely different state-of-the-art and safer approach.In this thesis, we have chosen to study the carcinogenesis, respectively its molecular mechanisms with computation methods based on quantum chemistry, hence using quantum mechanics. Unlike many others, the in silico approach for studying the molecular mechanisms of cancer does not pose any health risks. First, we performed alkylation and acylation reactions of carcinogen ß-propiolactone with the genetic material, more precisely with each DNA base (adenine, cytosine, guanine, and thymine) separately. The separate reactions of DNA bases have simplified and accelerated our calculations and enabled us to uncover the more voulnerable parts of our genetic material and thereby the most likely targets of chemical carcinogens. For a wider and more detailed insight into the molecular mechanisms of carcinogenesis, we have studied also the mechanisms of reactions between the chemical carcinogen acrylonitrile and the DNA bases.Next, using identical methods, we have additionally studied the reactions between the chemicalcarcinogen ß-propiolactone and the anticarcinogenic agents, namely glutathione (organism's scavenger molecule) and several polyphenolic substances that carry a potential for replacing glutathione and could therefore prevent carcinogenesis. All in all, we have shown that with the use of computational methods based on quantum chemistry we can not only study the carcinogenesis but additionally search for potential candidate molecules for its prevention and even cancer treatment. Moreover, the thesis provides a thorough review of numerous natural substances, like several polyphenols and various hop compounds, together with their known biological mechanisms of anticarcinogenic action and the advantages of their indigestion. The use of hops and its compounds dates back at least centuries or even a millennium. Currently, its part in the treatment of various diseases instead of only for dietary use is gradually raising.Last but not least, we aimed to uncover whether we can study the consequences of carcinogenesis, in our case single nucleotide polymorphisms, with the use of computational methods parametrized on quantum mechanics more precisely with the molecular dynamics simulations as well. Unlike the vast majority of the scientific community, we have chosen to study a less uncovered part of the genome – its noncoding part-by studying the effect of a regulatory single nucleotide polymorphism (rSNP) on the binding of a transcription factor essential for the expression of a specific gene on the regulation of this gene's expression. Even though genome-wide association studies (GWAS) imply that polymorphisms located in the noncoding part of the genome are linked with a higher risk for cancer, the noncoding part of the genome remains very poorly studied. We have proven that our approach can be used for studying the rSNPs and discovered numerous hindrances on the way to a successful and widespread cancer research that can be overcome and transformed into new opportunities and novel fields of cancer research.The thesis, therefore, encompasses all the cancer stages from its prevention through carcinogenesis and studies of its consequences, all the way to the prevention of carcinogenesis and non the least a natural approach to the healing of cancer. Studies of the mechanisms of carcinogenesis enable us to get better acquainted with cancer and consequentially to prevent it or even to more appropriately treat it. We are therefore pawing the way to the more successful cancer prevention and its treatm