Studies On The Interactions Between Several Carbamate Pesticides And DNA

According to previous studies, DNA interactions with small molecules of pesticides may produce DNA adducts, causing DNA damage or even changes the genetic information, so the study about the model of interaction between DNA and the carbamate pesticide has important significance. By simulating the physiological conditions (pH=7.4) in vitro, according to the experimental requirements, taking the ethidium bromide (EB), neutral red (NR) as the fluorescence and UV probe, using fluorescence, UV (ultraviolet), Nuclear magnetic resonance(NMR) and CD (circular dichroism) spectroscopy, combined with DNA melting experiments,polarization experiments, viscosity as well as the salt effect to study the binding mode of carbamate pesticides, Including Pirimicarb, Carbaryl, Propoxur, Aminocarb and Isoprocarb with calf thymus DNA, of the five carbamate pesticides, Select Pirimicarb and Carbaryl, combined with chemometric methods (ALS and PARAFAC) to further study the binding mode between pesticides and DNA, and Simulate the concentration of pesticides during the reaction, revealing the relationships between the binding mode and the pesticides'possible carcinogenic and mutagenic, which provide the experimental theoretical basis for the mechanism study between the interaction of pesticides and DNA and the development of newly high efficiency and low toxicity pesticides in the future. Through a series of experiments, the results of this study are summarized as follows:(1) A number of techniques have been employed to study the interaction of pirimicarb, carbaryl, propoxur, aminocarb, isoprocarb with DNA, including fluorescence, UV (ultraviolet) and CD (circular dichroism) spectroscopy, combined withΓions effect, DNA melting point and viscosity and further analysis of experimental determination of the five pesticides and DNA interaction model. The results showed that five pesticides were through the role of intercalation in the DNA nucleophilic sites, means that the five carbamate pesticides may formate DNA adducts after enter the organism, causing DNA damage by some degrees.(2) In physiological buffer, pH=7.40, take the use of fluorescence spectroscopy, DNA melting point and viscosity measurements and other experimental methods to discussed the impact of Cu2+, Ca2+on the interaction of DNA and pirimicarb, carbaryl, propoxur, The results showed that:the existence of Ca2+,Cu2+did not change the interaction pattern of pirimicarb, carbaryl, propoxur with DNA, but affected their interaction level in different degrees; When different aliquots of Cu2+,Ca2+were added to the different Binary system, their melting points slightly elevated, Which indicating that the presence of Cu+,Ca+could promote the binding of intercalative between DNA and pestiside; The trend of viscosity and the binding mode do not change when Cu+,Ca+exist, which were still increasing and intercalating; the Cu2+may influence the binding of propoxur and DNA in large degree and in higher temperature could benefit the interactionof propoxur and DNA.(3) Of all the five carbamate pesticides, Select Pirimicarb and Carbaryl, combined with chemometric methods (ALS and PARAFAC) to further study the binding mode between pesticides and DNA, and use nuclear magnetic resonance techniques to calculate the binding site in the the process of interaction between carbaryl with DNA.(4) This paper studied the relationship between the binding mode of calf thymus DNA and five kinds of carbamate pesticides, The binding constants of pirimicarb, carbaryl, propoxur, aminocarb, isoprocarb with DNA at 298K were calculated as 3.08×103,5.53x104,1.36×103,3.86×103 and 1.91×103 L-mol-1. By clarifying the way the interaction between DNA-pesticides'binding mode and DNA damage, the results revealed that there was a correlation between the binding mode and the carcinogenicity, mutagenicity of pesticides. The unwanted small molecules that intercalated into normal DNA may lead to the occurrence of DNA damage, and even further affecting the expression of genetic information. We believe that this study will provide useful information on the mechanism of carbamate pesticides binding to DNA and thus will be very helpful to the design of new pesticides with low toxicity.