Conformations of adducts and kinetics of binding to DNA of the optically pure enantiomers of anti-benzo(a)pyrene diol epoxide

Geacintov, Nicholas E.; Yoshida, Hiroko; Ibáñez, Víctor; Jacobs, Stephen A.; Harvey, Ronald G.

doi:10.1016/0006-291x(84)90435-2

Cited by 44 publications

(40 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these measurements the DNA molecules are oriented in a flow gradient utilizing a Couette cell (27), the characteristics of which have been described earlier (17). The dichroism in the region of the absorption band of the DNA and the phenanthrenyl chromophore is probed utilizing polarized light.…”

Section: Linear Dichroismmentioning

confidence: 99%

“…In buffer solution and in the absence of DNA, DE-I exhibits an absorption maximum at 305 nm (16). The appearance of a linear dichroism peak at 314 nm indicates that the physical DE-I•••DNA complex also exhibits an absorption maximum at 314 nm, since the LIA signal is proportional to the absorption spectrum when only one type of DNA complex is present (17). The 9 nm red shift, as well as the negative linear dichroism The linear dichroism spectra of the solutions change as the reaction proceeds (Fig.…”

Section: Kinetic Linear Dichroism Spectra and The Orientation Of The mentioning

confidence: 99%

“…A recently developed flow linear dichroism technique ( 17) is utilized to demonstrate that conformations of the physically bound diol epoxides change as the covalent binding Downloaded by [Rutgers University] at 22:46 05 April 2015 reaction takes place. The covalently bound phenanthrenyl chromophores have a conformation which is very different from those of the physical intercalation complexes, since the long axes of the covalently bound moieties are on the average tilted towards the axis of the DNA double helix.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conformations of Complexes Derived from the Interactions of Two Stereoisomeric Bay-Region 5-Methylchrysene Diol Epoxides with DNA

Kim

Roche

Geacintov

et al. 1986

Journal of Biomolecular Structure and Dynamics

Self Cite

View full text Add to dashboard Cite

The reaction mechanisms of two isomeric bay-region diol epoxides of 5-methylchrysene (trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II) with double-stranded DNA in aqueous solutions were studied utilizing kinetic flow dichroism and fluorescence techniques. As in the case of the previously studied benzo(a)pyrene-7,8-diol-9,10-oxide isomers (BaPDE), both DE-I and DE-II rapidly form intercalation-type complexes (association constants K = 2700 and 1500 M-1 respectively in a neutral 5mM phosphate solution). The physically bound diol epoxide molecules react on time scales of minutes to form predominantly tetraols; a greater fraction (6 +/- 1%) of DE-I than of DE-II (2-3%) molecules react with the DNA to form covalent products. The DE-II isomer is characterized by a greater reactivity than DE-I, and the rates of reaction are markedly accelerated in the presence of DNA in both cases. The linear dichroism spectra of the covalent adducts reveal that the conformations of both types of adducts are similar, with the long axes of the phenanthrenyl chromophores tilted, on the average, at angles of 38-52 degrees with respect to the average orientations of the transition moments (at 260 nm) of the DNA bases. The conformations of the covalently bound DE-I and DE-II molecules resemble those observed in the case of the highly tumorigenic (+) enantiomer of anti-BaPDE.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Linear Dichroismmentioning

confidence: 99%

Section: Kinetic Linear Dichroism Spectra and The Orientation Of The mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conformations of Complexes Derived from the Interactions of Two Stereoisomeric Bay-Region 5-Methylchrysene Diol Epoxides with DNA

Kim

Roche

Geacintov

et al. 1986

Journal of Biomolecular Structure and Dynamics

Self Cite

View full text Add to dashboard Cite

show abstract

“…UV spectroscopic studies and linear dichroism measurements are consistent with an intercalation process of BPDE [155]. The intercalated diol epoxide molecules are then protonated to yield triol carbonium ions which react with water and other cellular a. values are the average of determinations on two preparations; the amount of each adduct varied between 5 and 15 % in the two preparations; because DMBA 3,4-dihydrodiol was not radiolabeled, the depurination adducts could not be analyzed.…”

Section: F Interaction Between Bpt and Dna In Solid Water And Glass mentioning

confidence: 88%

“…Consequently, the implication of BPDEs in tumor initiation step is evidenced only by the covalent DNA adducts they form and, less convincingly, by their hydrolysis products, 7,8,9,10-tetrahydro-7,8,9,10-tetrahydroxybenzo[a]pyrene (BPT). Spectroscopic studies of the reaction of amn-BPDE with calf thymus DNA have demonstrated that BPDE is rapidly intercalated into the base pairs of DNA [28,155]. The intercalated complex is characterized by a 10 nm red-shift in its UV absoption maximum and its negative linear dichroism qjectrum.…”

Section: Fln Spectra Of Isomeric Bptsmentioning

confidence: 99%

High resolution fluorescence studies of metabolic pathways of DNA and oligonucleotide adducts from polycyclic aromatic compounds

Jeong

View full text Add to dashboard Cite

UMI MICROFILMED 1991 INFORMATION TO USERSThis manuscript has been reproduced from the microfflm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer.The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction.In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion.Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book.Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. 1991Signature was redacted for privacy.Signature was redacted for privacy.Signature was redacted for privacy.ii Ultraviolet and X-ray light have long beeHxknown to be highly cancer-causing and mutagenic agents [16]. For example, exposure of skin to UV light can induce skin cancer, while X-ray exposure to the thyroid induces thyroid cancer. Electromagnetic radiation, however, may not be assumed to cause all the cells in an exposed population to become cancerous since radiation can also produce many other deleterious changes leading to cell death. A radiation dose sufficient to induce cancer in all cells will virtually kill every cell. Not only can radiation induce simple mutation, it can also produce chromosome fragmentation, resulting in large deletions of genetic material. Thus radiation causes a variety of genetic changes, many of which might contribute to the cancerous state. A well known deleterious effect, xeroderma pigmentosum, is magnified in certain individuals. These people are homozygous for a recessive mutation that inactivates a gene involved in repairing thymine dimers, the major damage caused by UV Similar studies have shown that relatively weak carcinogens are also metabolized by monooxgenation mechanism. In most cases, however, the evidence is much less complete than in the case of B[a]P and rests primarily on comparison of the relative mutagenicities and tumorigenicities of the isomeric dihydrodiols or the corresponding diol epoxides obtained through synthesis. One-electron oxidation and metabolitesThe monooxygenation mechanism, which emphasizes the important role of the bay-region diol epoxide, has been widely accepted during last 15 years...

show abstract

Elucidating Structure–Function Relationships in Bulky DNA Lesions: From Solution Structures to Polymerases

Broyde

Wang

Patel

et al. 2010

The Chemical Biology of DNA Damage

View full text Add to dashboard Cite

Conformations of adducts and kinetics of binding to DNA of the optically pure enantiomers of anti-benzo(a)pyrene diol epoxide

Cited by 44 publications

References 13 publications

Conformations of Complexes Derived from the Interactions of Two Stereoisomeric Bay-Region 5-Methylchrysene Diol Epoxides with DNA

Conformations of Complexes Derived from the Interactions of Two Stereoisomeric Bay-Region 5-Methylchrysene Diol Epoxides with DNA

High resolution fluorescence studies of metabolic pathways of DNA and oligonucleotide adducts from polycyclic aromatic compounds

Elucidating Structure–Function Relationships in Bulky DNA Lesions: From Solution Structures to Polymerases

Contact Info

Product

Resources

About