Studies On The Toxic Interaction Mechanism Of Bisphenol A With DNA

Now environmental pollution has been one of the most pressing problems in the world, for which has caused a series of security problems and provokes heightened concern. Environmental endocrine disrupting chemicals (EDCs) is a pollutant can into the body by various ways which will cause endocrine system dysfunction in living organisms. And this will induce reproductive system damage, immunity dysfunction and neurological abnormality. In general, it may be released into the environment through human production and life activities. As an important component, DNA is the carrier of heredity information that encodes the genetic instruction in the development and functioning of all biology except few RNA viruses. EDCs can interact with the base pairs or phosphate group of nucleic acid, make it rupture and affect the gene’s function of adjust, control and expression, even lead to cancer.In this paper, we selected estrogen-like pollutant Bisphenol A (BPA) as study object, calf thymus DNA (ctDNA) and mouse hepatic cells as direct receptor, in vitro under physiological conditions investigated the toxicity mechanism of BPA and ctDNA at molecule level and cellular level, respectively. The article consists of the following two parts:In the first part, the influence factors between BPA and ctDNA and the genotoxicity effects of BPA to ctDNA were explored at molecular level by multi-spectroscopic techniques. Determined the inherent fluorescence of BPA was λex/λem=276nm/306nm. The concentration of BPA was lower than4×10-4mol L-1for this is critical value of BPA self-quenching. The fluorescence spectra results showed that ctDNA caused fluorescence quenching of BPA, which was confirmed as static quenching by fluorescent lifetime and quenching constant calculate. With pH increasing, the fluorescence quenching degree of ctDNA to BPA increased. And this change enhanced in acidic condition, which indicated that BPA and ctDNA didn’t combine with electrostatic mode. Moreover, UV-absorption spectra and the influence of ionic strength on the system of fluorescence further stated that there was intercalative binding between BPA and ctDNA. CD results also showed that BPA can change the conformation of DNA. In the second part, we investigated the DNA damage of male mice’s hepatic cells by comet assay and8-OHdG determine at cellular level. The results showed that BPA exposure increased the level of comet tail length, tail DNA percent, Olive tail moment and8-OHdG. Besides, the exposure time has the similar results in its alteration trend. This conclusion is consistent with molecular studies, which all suggested that BPA has genotoxicity to DNA, and can cause cellular DNA damage. In addition, this toxic effect has positive correlation with BPA concentration and response time.The results of our research indicate that BPA can induce DNA damage after it came into organism for which may insert DNA base pairs, resulting in a conformational change of DNA.