Abstract
2+ ) a common pollutant and known toxicant, and other various anti cancer drugs such as 5-fluorouracil bind to DNA competitively. Their efficacy as anti cancer drugs was brought by their mechanism of involvement with DNA and their interactive geometries. In this perspective we have designed CD spectral studies to investigate the interference of Pb 2+ with DNA-Drug interaction geometries. The change in elliptical intensities at around 260 nm to 280 nm and 245 nm shows the conformational changes in B-form of DNA. Amplitude changes observed with in B-form indicates the hairpin formation which is an intra-molecular variant of the B-form. Calf thymus DNA with 42% of G-C content has tendency towards hairpin transitions. In this study we have found that hairpin transitions might be involved in mechanism of Pb 2+
Highlights
Lead (Pb2+) is an ubiquitous metal that has been used by humans for more than 3 millionnia
In this study we have investigated the structural changes of calf thymus DNA brought by Lead (Pb2+) and 5-Fluoro Uracil (5-FU) individually and in combination under solvent affect
1ml working solution of Calf Thymus DNA sample was treated with 0.032 mM concentration of Lead Acetate and was titrated with 0.08 and 0.16 nM concentrations of drugs 5-Fluorouracil for a period of 1 Hour to study the interaction of Lead with Calf thymus DNA
Summary
Lead (Pb2+) is an ubiquitous metal that has been used by humans for more than 3 millionnia. Lead (Pb2+) accumulates in cell nuclei and associates with nuclear proteins and chromatin [3]. Lead (Pb2+) had been recognized as an environmentally toxic chemical, which causes a wide range of biological and biochemical consequences such as enzyme inhibition, fidelity of DNA synthesis, mutation, chromosome aberration, cancer and birth defects [4,5,6,7,8]. Interaction of Lead (Pb2+) with DNA can be of direct and indirect [9,10]. Direct interaction may involve covalent binding between Lead (Pb2+) and DNA. Indirect interaction may be associated with oxidative damage to DNA, thereby increasing cellular oxidants in the cells and producing free radicals. Indirect interaction involves the impairment of DNA repair processes via formation of DNA–protein and DNA–amino acid crosslinks [11]
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