Differential binding of chromium(VI) and chromium(III) complexes to salmon sperm nuclei and nuclear DNA and isolated calf thymus DNA

Abstract

The binding of CrCl3.6H2O, Cr(NO3)3.9H2O, [Cr(L-His)2] (NO3)3.H2O, [Cr(L-Cys)(L-His)].3.5H2O, [Cr(L-His)(D-Pen)].H2O, Na[Cr(L-Cys)2].2H2O, K2[Cr(GS)2].3H2O, Na2-CrO4.4H2O, and Na2Cr2O7.2H2O to salmon sperm nuclei and nuclear DNA was determined. The Cr(III)-amino acid complexes and Cr(VI) exhibited significantly lower Cr-nuclei and Cr-DNA binding levels relative to the inorganic complexes CrCl3.6H2O and Cr(NO3)3.9H2O. The binding of CrCl3.6H2O, Cr(NO3)3.9H2O and Na2Cr2O7.2H2O to salmon sperm nuclei and nuclear DNA in the presence of rat lung cytosol was determined under the same conditions. For those complexes studied in both buffer and cytosol, the Cr-DNA binding levels for Cr(III) complexes were higher in buffer than in cytosol, while a relatively higher binding level was observed for Cr(VI) in cytosol than in buffer. Slightly lower nuclear protein levels were present in Cr(VI) incubations than in Cr(III) incubations with nuclei both in the presence and the absence of cytosol. The relative binding of CrCl3.6H2O, Cr(NO3)3.9H2O, [Cr(L-His)2](NO)3.H2O, [Cr(L-Cys) (L-His)].3.5H2O, [Cr(L-His)(D-Pen)].H2O, Na[Cr(L-Cys)2].2H2O and Na2CrO4.4H2O to isolated calf thymus DNA in buffer was also determined. Positively charged, labile inorganic Cr(III) complexes, CrCl3.6H2O and Cr(NO3)3.9H2O, exhibited higher binding to DNA than [Cr(L-His) (D-Pen)].H2O, and no binding to DNA was observed with Cr(VI) and the other neutral, positively and negatively charged, inert Cr(III)-amino acid complexes. Although labile aquo chromium(III) complexes are quite reactive with DNA, the reactivity of chromium(III), formed upon intracellular reduction of carcinogenic chromium(VI), toward DNA will be diminished by complexation with cellular proteins, peptides and amino acids.

A Comparative Study of Calf Thymus DNA Binding to Cr(III) and Cr(VI) Ions

“…1, A and B, r ϭ 2). Our observations are consistent with other spectroscopic studies that showed no major Cr(VI)-DNA interaction in vitro in the absence of reducing agents (5,8,30). However, in the presence of metabolizing system, where Cr(VI) is reduced to Cr(III), major Cr(III)-DNA complexation has been observed (5,8,10,11).…”

Effects of Neutral, Cationic, and Anionic Chromium Ascorbate Complexes on Isolated Human Mitochondrial and Genomic DNA

“…The lymphocytes that were treated with Cr(III) showed no measurable DNA repair, even in the presence of vitamin C or catalase, the anti-oxidant reagents that prevent the extent of DNA migration. Although our results with cationic Cr(III) species are in accord with the literature outlined previously, [Cr(L-his) 2 ]NO 3 · H 2 O reportedly displays lower binding (Hneihen et al, 1993), while a negatively charged Cr(III)-saccharide complex cleaved the PSV neoplasmid (Rao et al, 1994). Obviously, further research is needed to clarify the mechanism of DNA damage.…”

“…1 and 2), it was deduced that Cr(VI), 1, 3, and 4 generated no observable damage above the biologically realistic levels. The following experiments were therefore continued with the active species (Cr 3+ (aq) and 2) toward physiological concentrations, considering the values that were applied in previous studies ranging from 0.1 mM to 3.0 mM (Luo et al, 1996;Tsou et al,1999;Capellmann and Bolt, 1992;Hneihen et al, 1993;Standeven and Wetterhahn, 1991;Stearns and Wetterhahn, 1997). Ascorbate is also present in millimolar concentrations in cellular systems (Horning, 1975).…”

“…Effect of the presence of amino acids It has been suggested that if chromium(III) complexes with cellular peptides, amino acids, and proteins, then its reactivity toward DNA will be greatly diminished (Hneihen et al, 1993). On the other hand, Beyersman and Köster (Beyersmann and Köster, 1987) showed that [Cr III gly 3 ] caused a significant level ), buffered with 10 × TE, pH = 8.0.…”

Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.

“…Melatonin has a high affinity for the nucleus (and possibly DNA itself), which may contribute to its protective effect against Cr-induced formation of 8-OH-dG. Cr(III) accumulates in nuclei and has a high affinity for DNA (52). Melatonin may prevent the formation of 8-OH-dG by displacing Cr(III) from the Cr-DNA binding complex and thereby reduce H202-mediated 'OH generation in the vicinity of DNA.…”