Chemical Linkage of Carcinogenic 3,4-Benzpyrene to DNA in Aqueous Solution induced by Peroxide and Iodine

Umans, Robert S.; Lesko, Stephen A.; Ts’o, Paul O. P.

doi:10.1038/221763a0

Cited by 22 publications

(2 citation statements)

References 9 publications

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“…The more reactive arene oxides would, however, if generated in situ, have excellent properties for binding to proteins and nucleic acids. The recent demonstration that covalent reaction of carcinogens with nucleic acids and proteins requires prior metabolism by the microsomal system (Gelboin, 1969) or chemical activation (Umans et al, 1969) is in line with these suggestions.…”

Section: Discussionmentioning

confidence: 65%

1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. V

Jerina¹,

Daly²,

Witkop³

et al. 1970

Biochemistry

432

153

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Section: Discussionmentioning

confidence: 65%

1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. V

Jerina¹,

Daly²,

Witkop³

et al. 1970

Biochemistry

432

153

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“…Some investigators have turned to model systems because conditions are more clearly defined and yields of products are greater than with in vivo systems. These investigators have approached the problem by activating carcinogens chemically or photochemically (4,5), or by adding a reactive derivative of the hydrocarbon, e.g., an epoxide, directly to DNA (6). The structure of any complex produced in these model systems, however, has not yet been fully characterized.…”

mentioning

confidence: 99%

Elucidation of hydrocarbon structure in an enzyme-catalyzed benzo[a]pyrene-poly (G) covalent complex.

Meehan¹,

Straub²,

Calvin³

1976

Proc. Natl. Acad. Sci. U.S.A.

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The carcinogen, benzo[alpyrene, was covalently attached to oly(G) by liver microsomes from rats pretreated with 3-mettylcholanthrene. The complex was hydrolyzed with enzymes or base and products were isolated by Sephadex chromatography. Absorbance and fluorescence spectra of the products fit that of a red-shifted pyrene aromatic system and suggest that metabolism has occurred at the 7-, 8-, 9-, and 10-positions of the hydrocarbon. Benzan 7,8-dihydroxy-7,8,9,10-tetrahydrobenzo[alpyrene; 9,10-diOH-4(H)l3aP, 9,10-dihydroxytetrahydro derivative of BaP; 7-OH-4(H)-BaP, 7-hydroxy-7,8,9,10-tetrahydrobenzo[ajpyrene; 9-OH-4(H)BaP and 10-OH-4(H)BaP, other monohydroxytetrahydro derivatives of BaP; 7-oxo-4(H) BaP,8,9,[ alpyrene; 8-oxo-4(H)BaP, 9-oxo-4(H)BaP and 10-oxo-4(H)BaP, other keto tetrahydro derivatives of BaP;7, (11,12) to the suggestion of a diol-epoxide intermediate in binding. Because of its sensitivity, fluorescence spectroscopy has been used in analyzing BaP-DNA complexes. The fluorescence emission spectrum of a complex formed in vivo that was consistent with that of a red-shifted pyrene nucleus (13) has been reported. This indicates that metabolism occurred at the 7-, 8-, 9-, and 10-positions of the hydrocarbon. Another study on the fluorescence of carcinogen-nucleic acid complexes has also appeared recently (14), but structural information was not obtained. In the above reports, fluorescence spectra were not corrected for wavelength-dependent distortions due to source, monochromators, and detector.In this investigation, corrected fluorescence spectra were made of a BaP-poly(G) complex and compared to that of known hydrocarbon derivatives. This approach has allowed us to describe definitive evidence for the structure of BaP after enzyme-catalyzed covalent binding to a nucleic acid. MATERIALS AND METHODS BaP

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The mechanism of binding of polycyclic aromatic hydrocarbons to nucleic acids: A theoretical investigation

Umans

Pullman

1971

Int J of Quantum Chemistry

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AbstractsA kinetic model employing calculated atom and bond localization energies to approximate relative activation energies of reaction is used to analyse previously obtained experimental results for in vitro and in vivo chemical binding of polycyclic aromatic hydrocarbons to nucleic acids. I t is found that in vitro linkage of hydrocarbons to DNA induced by a microsomal hydroxylating system is compatible with mechanisms involving either attack at the most reactive hydrocarbon center or attack at the most reactive hydrocarbon bond. Independent evidence leads us to favor the former mechanism. Further, the limited experimental data for in vivo linkage of hydrocarbons to DNA is found to be consistent with a model involving attack at the most reactive bond of the molecule: the "K region". This model is supported by a close parallelism found between extent of hydrocarbons bound to DNA in vivo and the experimentally determined relative reactivities of their K regions.

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Chemical Linkage of Carcinogenic 3,4-Benzpyrene to DNA in Aqueous Solution induced by Peroxide and Iodine

Cited by 22 publications

References 9 publications

1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. V

1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. V

Elucidation of hydrocarbon structure in an enzyme-catalyzed benzo[a]pyrene-poly (G) covalent complex.

The mechanism of binding of polycyclic aromatic hydrocarbons to nucleic acids: A theoretical investigation

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