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Conformational Changes in Nucleic Acids Modified by Chemical Carcinogens
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
D. Grunberger, I. B. Weinstein
Figure 18 shows that increasing extents of modification of native DNA with BPDE led to a progressive decrease in Tm during heat denaturation. The decrease in Tm was not linearly related to the percent of bases modified. When less than 1% of the bases were modified, no significant decrease in Tm could be detected (data not shown). In the range of 1 to 2% modification, the decrease in Tm was about 0.75°C per each 1% modification. In DNA with a 4.5% modification, the Tm was lowered by about 1.7°C for each 1% modification. The decrease in Tm was associated with a decrease in total hyperchromicity (Figure 18), suggesting that portions of the DNA duplex had undergone localized denaturation as a consequence of modification by BPDE.
Spectroscopy and Fluorimetry
Published in Joseph Chamberlain, The Analysis of Drugs in Biological Fluids, 2018
Some functional groups are lacking in useful absorption characteristics but when conjugated with a chromophore the wavelength of absorption and the intensity are both increased. Such groups are termed auxochromes and include hydroxyl functions, amines, and halogens. Increased intensity of absorptivity (hyperchromicity) and increased wavelength (bathochromicity) will also result if chromophores conjugate with one another.
Studies on the Interactions of HMG-1 and its Homologs with DNA
Published in Isaac Bekhor, Carol J. Mirell, C. C. Liew, Progress in Nonhistone Protein Research, 1985
Paul J. Isackson, David J. Cox, David Manning, Gerald R. Reeck
We have examined the thermal denaturation of poly(dA-dT) at three NaCl concentrations: 10, 50, and 150 mM. In each case, additional components of the solvent were 1 mM Tris-HCl/0.25 mM EDTA/1 mM dithiothreitol and the pH was 8.1. Figures 5 to 7 show denaturation profiles in 10, 50, and 150 mM NaCl, respectively, at several weight ratios of HMG-1 to poly(dA-dT). To allow several curves to be shown in each figure, the curves are offset arbitrarily without reindexing the ordinate. In each figure the ordinate is labeled “Absorbance”, but in several cases the curves result more from light scattering than from absorption. All curves in each figure result from heating samples of the same concentration of poly(dA-dT). If the only process contributing to the increase in apparent absorbance were the denaturation of poly(dA-dT), the increase should be nearly the same for all curves, regardless of the HMG-1-to-poly(dA-dT) ratio. (Any effect of HMG-1 on the hyperchromicity can be expected to be small.) In the curves in each figure, however, at sufficiently high HMG-1-to-poly(dA-dT) ratios, we see much larger increases in apparent absorbance than are seen in the absence of HMG-1. Thus, some process other than poly(dA-dT) denaturation is contributing to the increase in apparent absorbance. That process is the denaturation and aggregation of HMG-1, which results in light scattering.
Antiandrogen enzalutamide induced genetic, cellular, and hepatic damages: amelioration by triterpene Lupeol
Published in Drug and Chemical Toxicology, 2023
Mohammad A. Khan, Deepti Singh, Homa Fatma, Kafil Akhtar, Farruk Arjmand, Santosh Maurya, Hifzur R. Siddique
The DNA interaction studies performed to understand the mode of interaction of the compounds with ct-DNA suggested the interaction of Lupeol, Enzalutamide, and their combination with DNA. The absorption spectra of Enzalutamide and the combination showed a hyperchromic shift in UV-vis absorption studies with ct-DNA, suggesting the non-intercalative or electrostatic mode of binding. The observed hyperchromicity often results from a disruption in the secondary structure of duplex DNA, whereas hypochromicity is observed when the secondary structure of DNA is more stable (ct-DNA). Further, the observed redshift with increased absorption intensity in our study after the co-exposure suggests that Lupeol interferes with the binding of Enzalutamide to ct-DNA (Parveen et al.2016). These results were also confirmed by fluorescence and quenching studies, which supported the stronger binding of Enzalutamide and the combination of Lupeol and Enzalutamide through the electrostatic mode of binding.
In vitro cytotoxicity of polyphenols from Datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets
Published in Drug and Chemical Toxicology, 2020
Elham Chamani, Roshanak Ebrahimi, Khatereh Khorsandi, Azadeh Meshkini, Asghar Zarban, Gholamreza Sharifzadeh
Interaction of drugs or small molecules with the helix axis of DNA and conformational change increase the hyperchromicity of DNA. Its hyperchromicity will increase whenever drugs intercalate between the base pairs (Kashanian and Dolatabadi 2009). UV/vis spectroscopy results have shown that aqueous leaf-extract D. innoxia interacts with both phosphate groups and base pairs of DNA molecules. Mostafavinia and Hoshyar (2016) showed that rosemary extract interacts with ctDNA (calf thymus DNA) and increases its UV/vis absorbance at 260 nm, although this interaction with DNA was greater than the interaction of D. innoxia extract with DNA. Bathaie et al. (2007) demonstrated direct binding of carotenoids of saffron with minor groove of DNA that altered the DNA conformation (Bathaie et al. 2007).
The potential of ctDNA analysis in breast cancer
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
In 1989, Stroun et al. indicated the presence of tumor associated characteristics by DNA hyperchromicity in circulating DNA of cancer patients with various advanced malignancies, such as leukemia, lung, pancreatic, ovarian, kidney, and prostatic cancers [16]. Later, two main studies revealed the presence of NRAS and KRAS mutations in plasma of patients with acute myelogenous leukemia [17], and pancreatic cancer [18], respectively. Both studies suggested that specific tumor characteristics could be identified in circulation through cfDNA analysis. Apart from the presence of specific mutations, many other molecular alterations were revealed in plasma of cancer patients. In 1996, two groups simultaneously reported the presence of microsatellite alterations in plasma and serum of patients with small cell lung carcinoma (SCLC) [19] and head and neck squamous cell carcinoma (HNSCC) [20], respectively.