Study On The Mechanism Of DNA Related To Polycyclic Aromatic Hydrocarbons Derivatives And Tumor Diseases

Human extensive contact with various chemicals in the process of production and life, such as:all kinds of preservatives, coloring agents, car exhaust sulfides, nitrides, incomplete combustion of carbon-containing compounds produced by various types of toxic substances. All these toxic substances pollute the air, water and soil. With the rapid development of modern industry and a large gathering of the urban population, the amount of fossil fuels is also rapid growth, leading to increasingly serious environmental pollution, threatening human survival and health. Environmental pollution has become a global social nuisance, so that people’s living environment and sustainable development of the society is facing serious challenges. Previous studies indicate that environmental pollutants, such as particulate matter pollution, pollution of sulfur oxides, nitrogen oxides (NO) pollution, polycyclic aromatic hydrocarbons (PAHs) pollution, and heavy metal pollution can cause lung cancer and a series of cancer. With the further study of the mechanisms of carcinogenesis, the incidence of cancer has been demonstrated not only has a close relationship with the body’s internal environment but also the outer environment. The carcinogenic mechanisms of these contaminants is not yet entirely clear, some indirect carcinogens can become the ultimate carcinogens through the body’s metabolic transformation, DNA binding and persistence in the human body may be the decisive factors in carcinogenesis.In this work, we select a series of chrysene derivatives (6-hydroxychrysene,6-aminochrysene and6-nitrochrysene), using various spectroscopic methods and non-denaturing polyacrylamide gel electrophoresis to study its interaction with human tumor-related DNA fragments (p53DNA and C-myc DNA fragments) and different structures G-quadruplex formed by the human telomeric sequences, the impact on G-quadruplex structure conversion is also studied. We explain the mechanism of carcinogenicity of chrysene derivatives at the molecular level. The main results are as follows:(1) the binding mode of chrysene derivatives and double helix DNA is intercalative mode, the mode of interaction is depends on the planar structure of the benzene ring; the difference in substituent can only influence the binding capacity. The force type of the interaction between chrysene derivatives and double helix DNA is hydrogen bonding force and Van der Waals forces. The interaction has an impact on the base stacking and B-type conformation of double helix DNA.(2) The binding mode of chrysene derivatives and G-quadruplex is end-stacking mode and intercalative mode. Intramolecular G-quadruplex is more stable, it is difficult for small molecule insert two tetrad plane, the binding mode of chrysene derivatives and intramolecular G-quadruplex is end-stacking mode while the intermolecular G-quadruplex is less stable, the binding mode of chrysene derivatives and intermolecular G-quadruplex is intercalative mode. The different binding mode can hinder or facilitate G-quadruplex converted into the double helix DNA.(3) In the presence of complementary DNA strand, chrysene derivatives can hider intramolecular G-quadruplex converted into the double helix DNA.6-hydroxychrysene and6-aminochrysene can reduce the stability of intermolecular G-quadruplex, thus facilitate intermolecular G-quadruplex converted into the double helix DNA.