Environment Organic Pollutants And Tumor-associated Dna Interaction Studies

There are a wide variety of organic pollutants existed in the environment extensively, which posed a threat to human health and especially showed a high risk to tumor-related disease. In this paper, we chose three main kinds of environmental organic pollutants to study. In order to reveal the molecular mechanism of the organic pollutants with the human tumor-associated DNA, the interactions between pollutants and duplex DNA were investigated systematically by UV-vis spectrophotometry, fluorescence spectroscopy, circular dichroism, electrospray ionization mass spectroscopy techniques and molecular docking simulation measurements. Specific gene targets to the pollutant molecules were looked for, and the affinity and mode for different pollutants binding with the specific DNA molecules were identified, as well as the effect of the binding on the spatial structure of DNA. The results were discussed for the intrinsic link between human tumor diseases development and the pollutants at the molecular level, providing the basis of the environmental risk assessment of exogenous substances and the early warning of human tumor diseases.In this paper, organophosphorus pesticides, organochlorine pesticides, phenazine-1-carboxylic acid (PCA) and ciprofloxacin (CIP) were chosen to study on the interaction with telomere DNA, tumor suppressor gene p53 and C-myc oncogene promoter DNA, respectively. The main results were listed as following:(1) The UV and fluorescence titration experiments showed that the interaction of organophosphorus pesticides and telomere DNA was in a main intercalative mode, and the pesticides could lead to the DNA melting temperature decreased. The measurement of the apparent binding constants revealed that the order was:DIM> DDVP> OME. (2) The main mode of organochlorine pesticides with p53 DNA and C-myc DNA was intercalation, and pesticides could also decrease the DNA melting temperature. Meanwhile, the results of circular dichroism experiments showed that different organochlorine pesticides affected the spatial structure of DNA differently. In contrast, the binding abinity of DDD to P53 and that of DDT to C-myc were more stronger. (3) The UV, fluorescence and circular dichroism experiments ascertained the mode and affinity of CIP and PCA binding with telomere DNA. As the CIP for example, mass spectrometry experiments showed that the main binding mode between CIP and the telomere DNA was 1+1 form. Computer simulation of molecular docking experiments indicated that the binding site of CIP on the DNA fragment was probabily the DNA minor groove and had a certain preference to be close to the GC base pairs. The way of CIP binding with telomere DNA was interaction at the small groove of DNA, gone with hydrogen bonds and van der Waals interaction in the model.