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

Chromium(VI) salts are well known to be mutagens and carcinogens and to easily cross the cell membranes. Because they are powerful oxidizing agents, Cr(VI) reacts with intracellular materials to reduce to trivalent form, which binds DNA. This study was designed to investigate the interaction of calf thymus DNA with Cr(VI) and Cr(III) in aqueous solution at pH 6.5–7.5, using Cr(VI)/DNA(P) molar ratios (r) of 1:20 to 2:1 and Cr(III)/DNA(P) molar ratios (r) of 1:80 to 1:2. UV-visible and Fourier transform infrared (FTIR) difference spectroscopic methods were used to determine the metal ion-binding sites, binding constants, and the effect of cation complexation on DNA secondary structure. Spectroscopic results showed no interaction of Cr(VI) with DNA at low anion concentrations (r = 1:20 to 1:1), whereas some perturbations of DNA bases and backbone phosphate were observed at very high Cr(VI) contents (r > 1) with overall binding constant ofK = 508 m−1. Cr(III) chelates DNA via guanine N-7 and the nearest PO2 group with overall binding constant of K = 3.15 × 103m−1. Evidence for cation chelate formation comes from major shiftings and intensity variations of the guanine band at 1717 and the phosphate asymmetric stretching vibration at 1222 cm−1. At low Cr(III) concentration (r = 1:40), the number of Cr(III) ions bound to DNA were 6–7 cations/500 base pairs, and this increased to 30–35 cations/500 base pairs at high metal ion content (r = 1:4). DNA condensation occurred at high cation concentration (r = 1:10). No major alteration of DNA conformation was observed, and the biopolymer remained in the B family structure upon chromium complexation. Chromium(VI) salts are well known to be mutagens and carcinogens and to easily cross the cell membranes. Because they are powerful oxidizing agents, Cr(VI) reacts with intracellular materials to reduce to trivalent form, which binds DNA. This study was designed to investigate the interaction of calf thymus DNA with Cr(VI) and Cr(III) in aqueous solution at pH 6.5–7.5, using Cr(VI)/DNA(P) molar ratios (r) of 1:20 to 2:1 and Cr(III)/DNA(P) molar ratios (r) of 1:80 to 1:2. UV-visible and Fourier transform infrared (FTIR) difference spectroscopic methods were used to determine the metal ion-binding sites, binding constants, and the effect of cation complexation on DNA secondary structure. Spectroscopic results showed no interaction of Cr(VI) with DNA at low anion concentrations (r = 1:20 to 1:1), whereas some perturbations of DNA bases and backbone phosphate were observed at very high Cr(VI) contents (r > 1) with overall binding constant ofK = 508 m−1. Cr(III) chelates DNA via guanine N-7 and the nearest PO2 group with overall binding constant of K = 3.15 × 103m−1. Evidence for cation chelate formation comes from major shiftings and intensity variations of the guanine band at 1717 and the phosphate asymmetric stretching vibration at 1222 cm−1. At low Cr(III) concentration (r = 1:40), the number of Cr(III) ions bound to DNA were 6–7 cations/500 base pairs, and this increased to 30–35 cations/500 base pairs at high metal ion content (r = 1:4). DNA condensation occurred at high cation concentration (r = 1:10). No major alteration of DNA conformation was observed, and the biopolymer remained in the B family structure upon chromium complexation. Chromium(VI) salts are well known to be mutagens and carcinogens and to easily invade the insides of cells (1.De Flora S. Wetterhahn K.E. Life Chem. Rep. 1989; 7: 169-244Google Scholar). Cr(VI) produced DNA cross-links in rat tissues in vivo (2.Tsapakos M.J. Hamton T.H. Wetterhahn K.E. Cancer Res. 1983; 43: 5662-5667PubMed Google Scholar) and in cultured cellsin vitro (3.Tsapakos M.J. Hampton T.H. Sinclair P.R. Sinclair J.F. Bement W.J. Wetterhahn K.E. Carcinogenesis. 1983; 4: 959-966Crossref PubMed Scopus (45) Google Scholar, 4.Fornace Jr., A.J. Seres D.S. Lechner J.R. Harris C.C. Chem.-Biol. Interact. 1981; 36: 345-354Crossref PubMed Scopus (130) Google Scholar). Although Cr(VI) damaged nuclear DNA in whole cells, no reaction of Cr(VI) with isolated DNA occurred in vitro at physiological pH in the absence of a metabolizing system (5.Tsapakos M.J. Wetterhahn K.E. Chem.-Biol. Interact. 1983; 46: 265-277Crossref PubMed Scopus (176) Google Scholar). The Cr(VI) that is taken up is considered to be reduced by glutathione, cysteine, or ascorbic acid into Cr(III) (6.Connett P.H. Wetterhahn K.E. J. Am. Chem. Soc. 1985; 107: 4282-4288Crossref Scopus (202) Google Scholar), and the resulting cation reacts with DNA to form Cr(III)-DNA adducts. Because Cr(III) is a final form of chromium within the cell, the interaction of Cr(III) with DNA may play crucial role in the carcinogenetic action of Cr(VI) salts. The conversion of B form into Z form in the purine-pyrimidine sequence of DNA has been considered to be a factor in the transcriptional activity of genes (7.Razin A. Riggs A.D. Science. 1980; 210: 604-610Crossref PubMed Scopus (1541) Google Scholar). Cr(III) is found to interact with the poly(dG-dC) at low concentration and change B form to Z form in the presence of ethanol (8.Floro N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar). However, Cr(III) at high concentration causes DNA condensation, inhibiting the alteration of B to Z structure (8.Floro N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar). Moreover, the study on the effect of Cr(III) on DNA replication with single-stranded DNA template and micromolar concentration of Cr(III) revealed that Cr(III) bound in a dose-dependent manner to the template DNA and prevents DNA replication (9.Snow E.T. Xu L.S. Biochemistry. 1991; 30: 11238-11245Crossref PubMed Scopus (86) Google Scholar). However, if the unbound chromium was removed from the system by gel filtration, the rate of DNA replication by polymerase I (Klenow fragment) on the chromium-bound template increased more than 6-fold relative to control. This increase was paralleled by as much as a 4-fold increase in processivity and a 2-fold decrease in replication fidelity. When the concentration of Cr(III) increased further, DNA-DNA cross-links occurred to inhibit the polymerase activity. Trivalent chromium can bind purified DNA and form lesions capable of obstructing DNA replication in vitro (10.Bridgewater L.C. Manning F.C. Woo E.S. Patierno S.R. Mol. Carcinog. 1994; 9: 122-133Crossref PubMed Scopus (114) Google Scholar, 11.Bridgewater L.C. Manning F.C. Patierno S.R. Carcinogenesis. 1994; 15: 2421-2427Crossref PubMed Scopus (109) Google Scholar). It has also been observed that intact Novikoff ascites hepatoma cells exposed to potassium chromate formed cross-linking of nuclear proteins to DNA (12.Wedrychowski A. Ward W.S. Schmidt W.N. Hnilica L.S. J. Biol. Chem. 1985; 260: 7150-7155Abstract Full Text PDF PubMed Google Scholar). Recently, Cr(III) was shown to cause mutational spectrum in shuttle vector systems replicated in human cells (13.Tsou T.C. Lin R.J. Yang J.L. Chem. Res. Toxicol. 1997; 10: 962-970Crossref PubMed Scopus (58) Google Scholar). Thus, the interaction of Cr(III) with DNA may be responsible for carcinogenic activity of chromium. There are many agents that are specific for guanine alkylation in the O-6, N-7, or C-8 position. Several of these are highly active carcinogens, such asN-acetoxy-N-2-acetylaminofluorene, which alkylates in the C-8 position, and nitrosoamines, nitrogen mustards, nitrourea, and aflatoxin, which alkylate on the N-7 position (14.$$$$$$ ref data missingGoogle Scholar). The action of certain carcinogens, e.g. modification of guanine by N-7 methylation or by alkylation at C-8 withN-acetoxy-N-2-acetylaminofluorene facilitated the B to Z transition of poly(dG-dC) (15.Moller A. Nordheim A. Nichols S.R. Rich A Proc. Natl. Acad. Sci. U. S. A. 1981; 78: 4777-4781Crossref PubMed Scopus (66) Google Scholar, 16.Santella R.M. Grunberger D. Weinstein I.B. Rich A. Proc. Natl. Acad. Sci. U. S. A. 1981; 78: 1451-1455Crossref PubMed Scopus (126) Google Scholar, 17.Sage E. Leng M. Proc. Natl. Acad. Sci. U. S. A. 1980; 77: 4597-4601Crossref PubMed Scopus (125) Google Scholar). On the contrary, modification of poly(dG-dC) with the antitumore drugcis-diamine-dicholoplatinum (II) (a cross-linking agent) prevented the B to Z conversion (18.Malfoy B. Hartmann B. Leng M. Nucleic Acids Res. 1981; 9: 5659-5669Crossref PubMed Scopus (59) Google Scholar, 19.Ushay H.M. Santella R.M. Caradonna J.P. Grunberger D. Lippard S.J. Nucleic Acids Res. 1982; 10: 3573-3587Crossref PubMed Scopus (43) Google Scholar). It was found that Cr(III) preferentially binds guanine-containing DNAs (5.Tsapakos M.J. Wetterhahn K.E. Chem.-Biol. Interact. 1983; 46: 265-277Crossref PubMed Scopus (176) Google Scholar, 20.Wolf T. Kasemann R. Ottenwalder H. Carcinogenesis. 1989; 10: 655-659Crossref PubMed Scopus (51) Google Scholar). The results of a study on the DNA replication system showed that most of Cr(III) binding to the single-stranded template DNA is electrostatic because 40% or more of bound cation could be displaced by high salt wash, whereas only 20% or less chromium is chelatable by EDTA (9.Snow E.T. Xu L.S. Biochemistry. 1991; 30: 11238-11245Crossref PubMed Scopus (86) Google Scholar). In the present study, we have investigated the complexation of Cr(III) and Cr(VI) with calf thymus DNA using UV-visible and FTIR 1The abbreviations used are: FTIR, Fourier transform infrared. difference spectroscopy at pH 6.5–7.5 with Cr(III)/DNA(P) of 1:80 to 1:2 and Cr(VI)/DNA(P) of 1:20 to 2:1. Structural analysis regarding the chromium-binding sites, binding constants, and the alteration of DNA secondary structure are reported here. This is a first infrared spectroscopic study regarding the Cr(III)-DNA chelate formation and should help to elucidate the nature of the carcinogenic potential of chromium. Highly polymerized type I calf thymus DNA sodium salt (7% sodium content) was purchased from Sigma and was deproteinated by the addition of CHCl3 and isoamyl alcohol in NaCl solution. Crystalline CrCl3(H2O)6 and K2CrO4 salts were of reagent grade. Sodium DNA was dissolved to 1% w/w (25 mm DNA(phosphate)) in 50 mm NaCl and 1 mm sodium cacodylate (pH 7.30) at 5 °C for 24 h with occasional stirring to ensure the formation of a homogeneous solution. The appropriate amount of CrCl3(H2O)6 and K2CrO4 (0.3 to 10 mm) was prepared in distilled water and added dropwise to DNA solution to attain desired Cr(III)/DNA(P) molar ratios of 1:80, 1:40, 1:20, 1:10 1:4, and 1:2 and Cr(VI)/DNA(P) molar ratios of 1:20, 1:10, 1:5, 1:1, and 2:1 at a final DNA concentration of 0.5% w/w or 12.5 mm DNA(phosphate). The pH values of solutions were adjusted to 6.5–7.5, using NaOH solution. The infrared spectra were recorded 2 h after mixing of chromium salt and DNA solutions. The infrared spectra of Cr(III)-DNA complexes with r = 1:2 could not be recorded as solution because of solid gel formation. When UV absorption spectra were recorded, solutions containing DNA at a final concentration of 6.25 mm phosphate and 50 mmNaCl were used. The mixtures containing calf thymus DNA (6.25 mm of phosphate) and Cr(III) at molar ratios of 1:40 to 1:4 in 50 mm NaCl were applied to Sephadex G-25 (0.8 × 4.5 cm) column equilibriated in water, and 20 fractions were collected. The concentrations of Cr(III) and DNA in each fraction were determined by atomic absorption spectroscopy at 357.9 nm and by UV at 260 nm. The concentrations of Cr(III)-DNA complexes in each mixture were analyzed from regions where elution patterns of Cr(III) and DNA overlapped. Infrared spectra were recorded on a Bomem DA3–0.02 FTIR spectrometer equipped with a nitrogen cooled HgCdTe detector and KBr beam splitter. The solution spectra were taken using AgBr windows with resolution of 2–4 cm−1 and 100–500 scans. Each set of infrared spectra were taken (three times) on three identical samples with the same DNA and metal ion concentrations. The water subtraction was carried out with 0.1 m NaCl solution used as a reference at pH 6.5–7.5 (21.Alex S. Dupuis P. Inorg. Chim. Acta. 1989; 157: 271-281Crossref Scopus (202) Google Scholar). A good water subtraction was achieved as shown by a flat base line around 2200 cm−1where the water combination mode is located. This method is a rough estimate but removes the water content in a satisfactory way. The difference spectra ((DNA solution + chromium solution) − (DNA solution)) were produced, using a sharp DNA band at 968 cm−1 as internal reference. This band, because of deoxyribose C-C stretching vibrations, exhibits no spectral changes (shifting or intensity variations) on Cr-DNA complexation, and it was cancelled upon spectral subtraction. The spectra were smoothed with a Savitzky-Golay procedure (21.Alex S. Dupuis P. Inorg. Chim. Acta. 1989; 157: 271-281Crossref Scopus (202) Google Scholar). The intensity ratios of several DNA in-plane vibrations related to A-T and G-C base pairs and the PO2 stretchings were measured (with respect to the reference band at 968 cm−1) as a function of chromium concentration with an error of ±3%. These intensity ratios were used to calculate binding constants of Cr(III) with DNA bases and the backbone phosphate group. UV absorption spectra were recorded on a Hewlett Packard 8452A Diode Array Spectrophotometer. The chromium concentrations were determined using atomic absorption Perkin-Elmer Aanalyst 100 Spectrometer. At r = 1:20 to 1, Cr(VI) does not bind to DNA in aqueous solution. Evidence for this comes from the lack of major spectral changes (intensity or shifting) of the prominent DNA in-plane vibrations (21.Alex S. Dupuis P. Inorg. Chim. Acta. 1989; 157: 271-281Crossref Scopus (202) Google Scholar, 22.Keller P.B. Hartman K.A. Nucleic Acids Res. 1986; 14: 8167-8182Crossref PubMed Scopus (42) Google Scholar, 23.$$$$$$ ref data missingGoogle Scholar, 24.Loprete Hartman K.A. Biochemistry. PubMed Scopus Google Scholar, 1991; Scopus Google Scholar, S. J. J. J. Chem. Scopus Google Scholar, B. Jr., 1984; PubMed Scopus Google Scholar, E. J. in Infrared and Scholar) at 1717 and 1222 PO2 and However, at high chromate concentration (r > some perturbations of DNA vibrations were The guanine band at 1717 a at whereas the band at a at cm−1 the band at observed at cm−1 in the presence of chromate anion 1 r = The phosphate asymmetric stretching vibration at 1222 cm−1 of the DNA was a at cm−1 as Cr(VI) concentration increased r = at cm−1 and cm−1 in the difference spectra of complexes is from in the intensity of DNA vibrations and bases and backbone phosphate) 1 The observed spectral changes are to interaction water of on the DNA and of the The with the chromate anion and the presence of a on the backbone PO2 group are the major for a complexation. It should be that the presence of a band at cm−1 in the infrared which at cm−1 in the difference spectra of the complexes are to the vibrations Infrared of and Scholar) and r = are with spectroscopic that showed no major interaction in vitro in the absence of agents (5.Tsapakos M.J. Wetterhahn K.E. Chem.-Biol. Interact. 1983; 46: 265-277Crossref PubMed Scopus (176) Google Scholar, N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar, Wetterhahn K.E. Carcinogenesis. 14: PubMed Scopus (45) Google Scholar). However, in the presence of metabolizing where Cr(VI) is reduced to major Cr(III)-DNA complexation has been observed (5.Tsapakos M.J. Wetterhahn K.E. Chem.-Biol. Interact. 1983; 46: 265-277Crossref PubMed Scopus (176) Google Scholar, N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar, L.C. Manning F.C. Woo E.S. Patierno S.R. Mol. Carcinog. 1994; 9: 122-133Crossref PubMed Scopus (114) Google Scholar, 11.Bridgewater L.C. Manning F.C. Patierno S.R. Carcinogenesis. 1994; 15: 2421-2427Crossref PubMed Scopus (109) Google variations for several DNA in-plane vibrations at 1717 and and and and 1222 cm−1 as a function of Cr(VI) concentration Cr(VI)/DNA(P) molar At low cation concentrations (r = 1:80 to Cr(III) binds DNA guanine and the backbone PO2 group. Evidence for this comes from major spectral shiftings of the at 1717 cm−1 and at 1222 cm−1 asymmetric (21.Alex S. Dupuis P. Inorg. Chim. Acta. 1989; 157: 271-281Crossref Scopus (202) Google Scholar, 22.Keller P.B. Hartman K.A. Nucleic Acids Res. 1986; 14: 8167-8182Crossref PubMed Scopus (42) Google Scholar, 23.$$$$$$ ref data missingGoogle Scholar, 24.Loprete Hartman K.A. Biochemistry. PubMed Scopus Google Scholar, 1991; Scopus Google Scholar, S. J. J. J. Chem. Scopus Google Scholar, B. Jr., 1984; PubMed Scopus Google Scholar, E. J. in Infrared and Scholar). The guanine band at 1717 cm−1 a at cm−1 and the phosphate band at 1222 cm−1 was observed at upon Cr(III) complexation 1 In a major increase in the intensity of guanine band at 1717 and PO2 band at 1222 cm−1 was observed as Cr(III) concentration increased to r = 1:20 The at and cm−1 in the difference spectrum of the Cr-DNA complexes are to a increase of the intensity of DNA bases and the at low Cr(III) concentration (r = 1 However, as cation concentration = 1:20, the in the difference spectrum of Cr-DNA complexes in for the guanine band at and the PO2 band at cm−1 1 r = In the relative intensity ratios of the cm−1) and cm−1) have from to The observed spectral shiftings = to cm−1) and the major intensity variations for the guanine band at 1717 cm−1 and the PO2 vibration at 1222 cm−1 are to the cation via guanine N-7 and the backbone phosphate group 1 B and r = It has been that the infrared spectral changes related to the DNA in-plane vibrations at cm−1 are to the metal interaction guanine N-7 (21.Alex S. Dupuis P. Inorg. Chim. Acta. 1989; 157: 271-281Crossref Scopus (202) Google Scholar, 22.Keller P.B. Hartman K.A. Nucleic Acids Res. 1986; 14: 8167-8182Crossref PubMed Scopus (42) Google Scholar). It should be that a intensity variations were observed for the band at and band at no major spectral shiftings for this vibration occurred upon Cr(III) complexation 1 A and Thus, the amount of chromium that binds to the A-T base is whereas an cation binding to the A-T bases be The of the overall binding constants were carried out using UV spectroscopy as reported Biochemistry. Scopus Google Scholar). the for chromium cation and DNA is as in 1, the binding constants of chromium cation complexes with DNA can be as in 1 2 The of is and the binding constant is from the of the on the to the Biochemistry. Scopus Google Scholar). of chromium were determined by of DNA at nm from of DNA. of cation were determined by of chromium from chromium used for the data of increased as a function of and overall binding constants for and Cr(III)-DNA were to = 508 = 3.15 × Because the Cr(III)-DNA interaction guanine N-7 and the backbone PO2 the binding constants of Cr(III) with guanine and backbone PO2 were determined from the intensity ratios of DNA in-plane vibrations related to guanine cm−1) and backbone phosphate cm−1) the data from DNA and Cr(III)-DNA formed at r = 1:10, the binding constants were to be = × = × 103m−1. The binding constants for and bases were much than of the guanine and phosphate group. This that the interaction of Cr(III) with the A-T base is In a study, on the intensity variations of the infrared absorption the binding constants of the complexes were where was to the backbone PO2 group and the guanine N-7 J.F. Biophys. J. Full Text Full Text PDF PubMed Scopus Google Scholar). The low = of the cation chelate complexes are to the nature of the It has been that most of Cr(III) binding to the single-stranded template DNA is electrostatic because 40% or more of bound cation could be displaced by high salt wash, whereas only 20% or less of the chromium is chelatable by EDTA (9.Snow E.T. Xu L.S. Biochemistry. 1991; 30: 11238-11245Crossref PubMed Scopus (86) Google Scholar). On the the overall binding constant for was to be a low of the complexes is of no interaction in aqueous solution. on the data from UV of Cr(III) bound to DNA were to be cations/500 base pairs = 1:40 and cations/500 base pairs = 1:4 the of Cr(III) bound to DNA by the mixtures were to Sephadex G-25 column (0.8 × 4.5 cm) in aqueous and concentrations of Cr(III)-DNA complexes were determined by atomic absorption and UV absorption spectroscopic The of Cr(III) bound to DNA were to be cations/500 base pairs at r = 1:40 and cations/500 base pairs at group (13.Tsou T.C. Lin R.J. Yang J.L. Chem. Res. Toxicol. 1997; 10: 962-970Crossref PubMed Scopus (58) Google Scholar) showed that Cr(III) bound to of a DNA at a low concentration of in the presence of 10 mm potassium phosphate (pH whereas the number increased to 100 in the presence of and Thus, the number of Cr(III) bound to DNA could be by the solution and The of Cr(III) bound to calf thymus DNA were less than bound to a DNA (13.Tsou T.C. Lin R.J. Yang J.L. Chem. Res. Toxicol. 1997; 10: 962-970Crossref PubMed Scopus (58) Google Scholar). This may be to the NaCl concentration mm) used in DNA with respect to DNA solution which the and the Cr(III) to At cation concentration (r = 1:10 and Cr(III) DNA Evidence for this comes from a major decrease in the intensity of the at 1717 and 1222 DNA condensation by Cr(III) ions is well investigated using R. A. J. 1984; PubMed Scopus Google Scholar). The condensation of DNA at r = 1:10 and up to r = R. A. J. 1984; PubMed Scopus Google Scholar). However, because of the solid gel formation of DNA solution in the presence of Cr(III) at high cation content (r = the infrared spectra of complexes formed at high cation concentration could not be recorded as solution. It was considered that the condensation of DNA by of DNA by Biophys. PubMed Scopus Google Scholar). study with that the binding of the cation to the backbone phosphate group causes DNA condensation J. J. Mol. Biol. 1980; PubMed Scopus Google Scholar). infrared spectroscopic study with showed that binding of the cation to guanine N-7 and the backbone phosphate that may for DNA infrared spectroscopic results showed that Cr(III) and Cr(VI) not DNA changes from B to A or B to Z structure. Evidence for this comes from no major of the DNA at cm−1 stretching a 1 In a B to A the DNA infrared at and 1717 cm−1 were at and whereas the backbone PO2 asymmetric stretching at 1222 cm−1 a at cm−1 Hartman K.A. Biochemistry. PubMed Scopus Google Scholar, E. J. in Infrared and Scholar, J.F. M. PubMed Scopus Google Scholar). In a B to Z the infrared at 1717 and cm−1 were observed at and whereas the PO2 band at 1222 cm−1 was displaced a at cm−1 Hartman K.A. Biochemistry. PubMed Scopus Google Scholar, E. J. in Infrared and Scholar, J.F. M. PubMed Scopus Google Scholar). spectral changes not for DNA in the presence of Cr(III) and Cr(VI) 1 The major of the at 1717 to cm−1 and 1222 to cm−1 in the spectra of the Cr(III)-DNA complexes are to the Cr(III) to guanine N-7 and backbone phosphate group 1 spectroscopic also showed that chromium inhibit B to A or B to Z changes upon DNA complexation (8.Floro N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar). However, at low cation Cr(III) can B to Z transition for in the presence of ethanol (8.Floro N.A. Wetterhahn K.E. Biochem. Biophys. Res Commun. 1984; 124: 106-113Crossref PubMed Scopus (12) Google Scholar). On the of spectroscopic results of calf thymus DNA in the presence of Cr(VI) and Cr(III) metal ions in aqueous the can be No interaction was observed in whereas Cr(III) chelates DNA guanine N-7 and the backbone phosphate The low of the Cr(III)-DNA is to the nature of the Cr(III) DNA condensation at high cation and Cr(VI) and Cr(III) ions not DNA changes at low or high cation

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