An FIRT spectroscopic study ofcalf thymus DNA complexation with Al(III) and Gal(III) cations
The interaction of calf-thymus DNA with trivalent Al and Ga cations, in aqueous solution at pH = 6-7 with cation/DNA(P) (P = phosphate) molar ratios (r) 1/80, 1/40, 1/20, 1/10, 1/4 and 1/2 was characterized by Fourier Transform infrared (FTIR) difference spectroscopy. Spectroscopic results show the formation of several types of cation-DNA complexes. At low metal ion concentration (r = 1/80, 1/40), both cations bind mainly to the backbone PO2 group and the guanine N-7 site of the G-C base pairs (chelation). Evidence for cation chelate formation comes from major shifting and intensity increase of the phosphate antisymmetric stretch at 1222 cm-1 and the mainly guanine band at 1717 cm-1. The perturbations of A-T base pairs occur at high cation concentration with major helix destabilization. Evidence for cation binding to A-T bases comes from major spectral changes of the bands at 1663 and 1609 cm-1 related mainly to the thymine and adenine in-plane vibrations. A major reduction of the B-DNA structure occurs in favor of A-DNA upon trivalent cation coordination.
Available from: Ferdinando Mannello
- "The involvement of oestrogen in the development of breast cancer is well established (Miller, 1996) and Al is a metalloestrogen (Darbre, 2006b). However, Al can bind to DNA (Karlik et al., 1980; Ahmad et al., 1996; Zhang et al., 2002), modulating its topology (Latha et al., 2002), is known to be genotoxic (Lukiw et al., 1998; Exley, 1998) and has been shown to be carcinogenic in animal studies (Anghileri et al., 2000). It also has pro‐oxidant effects (Exley, 2004) and might contribute to oxidative stress through its interference with the action of transcription factors such as HIF‐1 and NF‐κB because of its ability to occupy key zinc binding sites essential for the function of zinc finger transcription factors (Exley, 2001). "
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ABSTRACT: Aluminium is not a physiological component of the breast but has been measured recently in human breast tissues and breast cyst fluids at levels above those found in blood serum or milk. Since the presence of aluminium can lead to iron dyshomeostasis, levels of aluminium and iron-binding proteins (ferritin, transferrin) were measured in nipple aspirate fluid (NAF), a fluid present in the breast duct tree and mirroring the breast microenvironment. NAFs were collected noninvasively from healthy women (NoCancer; n = 16) and breast cancer-affected women (Cancer; n = 19), and compared with levels in serum (n = 15) and milk (n = 45) from healthy subjects. The mean level of aluminium, measured by ICP-mass spectrometry, was significantly higher in Cancer NAF (268.4 ± 28.1 μg l(-1) ; n = 19) than in NoCancer NAF (131.3 ± 9.6 μg l(-1) ; n = 16; P < 0.0001). The mean level of ferritin, measured through immunoassay, was also found to be higher in Cancer NAF (280.0 ± 32.3 μg l(-1) ) than in NoCancer NAF (55.5 ± 7.2 μg l(-1) ), and furthermore, a positive correlation was found between levels of aluminium and ferritin in the Cancer NAF (correlation coefficient R = 0.94, P < 0.001). These results may suggest a role for raised levels of aluminium and modulation of proteins that regulate iron homeostasis as biomarkers for identification of women at higher risk of developing breast cancer. The reasons for the high levels of aluminium in NAF remain unknown but possibilities include either exposure to aluminium-based antiperspirant salts in the adjacent underarm area and/or preferential accumulation of aluminium by breast tissues.
Available from: kcl.ac.uk
- "However, another possible source of DNA-damaging chemicals could be the antiperspirant agents themselves, the aluminium and zirconium salts (Laden and Felger, 1988). There is evidence that aluminium can bind to DNA (Karlik et al. , 1980; Ahmad et al. , 1996). Recent data report a relatively strong binding of Al(III) to DNA, which occurs with the phosphate backbone of the DNA under neutral pH conditions (Zhang et al. , 2002). "
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ABSTRACT: Although risk factors are known to include the loss of function of the susceptibility genes BRCA1/BRCA2 and lifetime exposure to oestrogen, the main causative agents in breast cancer remain unaccounted for. It has been suggested recently that underarm cosmetics might be a cause of breast cancer, because these cosmetics contain a variety of chemicals that are applied frequently to an area directly adjacent to the breast. The strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells. Multidisciplinary research is now needed to study the effect of long-term use of the constituent chemicals of underarm cosmetics, because if there proves to be any link between these cosmetics and breast cancer then there might be options for the prevention of breast cancer.
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ABSTRACT: Metal-mediated base pairs by the interaction between metal ions and artificial bases in oligonucleotides have been developed for their potential applications in nanotechnology. We recently found that a natural T:T mismatched base pair bound with Hg2+ ion to form a novel T–Hg–T base pair. Here, we examined the thermodynamic properties of the binding between Hg2+ and each of the single and double T:T mismatched base pair duplex DNAs by isothermal titration calorimetry. Hg2+ specifically bound with the T:T mismatched base pair at 1:1 molar ratio with 106M−1 binding constant, which was significantly larger than those for nonspecific metal ion–DNA interactions. In the Hg2+–double T:T mismatched base pair interaction, the affinity for the second Hg2+ binding was significantly larger than that for the first Hg2+ binding. The positively cooperative binding may be favorable to align multiple Hg2+ in duplex DNA for the application of the metal-mediated base pairs in nanotechnology.
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