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Interaction Between Pollutants And Human Tumor-associated DNA Of BTEX Environment

Posted on:2014-07-21Degree:MasterType:Thesis
Country:ChinaCandidate:L LiFull Text:PDF
GTID:2264330401969309Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
Organic compounds have wide varieties, which are commonly used as main human subsistence in daily life, such as clothing dyes, food additives, vehicle fuel, daily necessities colorants, plasticizers and etc. Coupled with the applications, organic materials, on the other hand, will become pollutants and cause bad impact on human life. For example, vehicle exhaust pollution, food safety issues, climate anomalies and so on. This can be said that everything in the living environment will be exposed to various types of organic matter so it’s a threat to human health. In current times, the various environmental organic pollutants and their relationship with the tumor-associated diseases attract widespread concern. Cancer is a disease caused by genes, which are tightly associated with human tumor-associated DNA, that’s proto-oncogenes and tumor suppressor genes. The proto-oncogene involves in promoting cell growth and mitosis, it is the precursor of the oncogene. On the other hand, tumor suppressor gene is responsible for the inhibition of cell growth, regulation of cell division. When the damage or mutation of genes regulating cell growth occurs, cells will lose control and produce tumors.In our study three types of organic pollutants are selected:polycyclic aromatic hydrocarbons derivatives (PAHs,1-hydroxypyrene.1-amino-pyrene,1-pyrene butanol,1-pyrene butylamine); Polychlorinated Biphenyls (PCBs, trichlorobiphenylpolychlorinated biphenyls, pentachlorobiphenyl. hexachlorobiphenyl); the daily additive (Triclosan, Bisphenol A), and two important rumor-associated DNA fragments (p53and C-myc promoter fragment).We use a variety of spectroscopic methods and the technology of polyacrylamide gel electrophoresis to study the interaction mechanism at the molecular level, also aim at exploring the role played by different structure of the organic pollutants (the type of functional group, the length of the functional group, the location of the functional groups and the molecular plane) on DNA of different sequences.We get the main results as follows:(1) Polycyclic aromatic hydrocarbons derivatives interact with DNA maily via intercalation, short-chain substituented PAHs have better delocalization of conjugated π-π, and long-chain substituented can increase the molecular polarity, both of which can cause the intercalation complex stabilitv to increase.-OH substituted PAHs molecules interact with DNA by groove binding and intercalative, while-NH2substituted PAHs mainly by electrostatic and intercalative, the binding forces are hydrogen bonds and van der Waals forces.(2) Poly chlorinated Biphenyls play non-covalent interactions on human tumor-associated DNA, and their main mode are intercalation and electrostatic interactions, PCBs have similar plane structure, offering the possibility of intercalation, and owning to the Cl atoms connected on the ring, the PCBs have a positive electrostatic potential, so electrostatic interaction present when interacted with DNA, that is multiple forces of PCBs affect the normal conformation of DNA.(3) Triclosan interacts with the two human tumor-associated DNA by partially embedding into the groove of the double helix, and triclosan shows slightly stronger binding capacity on the tumor suppressor gene p53gene P1promoter region than C-myc gene promoter NHE III1region, so that the DNA double helix structure gets changed. Bisphenol A interacts with the two human tumor-associated DNA via intercalation and electrostatic interactions, the binding decreases the content of double-stranded conformation and affects the structure of the double helix.
Keywords/Search Tags:Human tumor-associated DNA, polycyclic aromatic hydrocarbonsderivatives, polychlorinated biphenyls, Environmental Endocrine Disruptors, non-covalent interactions, spectroscopy, gel electrophoresis
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