Formation of DAN-binding products from isolated benzo[a]pyrene metabolites in rat liver nuclei

Jernström, Bengt; Vadi, Helena; Orrenius, Sten

doi:10.1016/0009-2797(78)90109-6

Cited by 30 publications

(9 citation statements)

References 24 publications

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“…In contrast to the 7,8-diol, the 9,10-diol derivative yields on further metabolism a triol rather than a diol-epoxide, and this triol is also thought to have the additional phenolic OHgroup in the 1-or 3-positions (THAKKER et al 1978;MOORE and COHEN 1978). 9-HydroxyBaP, which can be involved in metabolic activation in some situations, yields the related 4,5-oxide and 4,5-diol as well as two products tentatively identified as the 4,9-and 5,9-diphenols when incubated with rat liver preparations (JERNSTROM et al 1978) through metabolism at the K-region 4,5-bond. Recent work on the further metabolism of 3-hydroxyBaP in rats has shown that conjugates of the 3-hydroxyBaP 7,8-diol and the 3,5-diphenol are excreted in bile (RIBEIRO et al 1985), although again it is not clear in what order the conjugation and/or further metabolism reactions occur.…”

Section: Hydroxylated Products -Further Metabolismmentioning

confidence: 98%

Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation

Hall¹,

Grover²

1990

Handbook of Experimental Pharmacology

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Section: Hydroxylated Products -Further Metabolismmentioning

confidence: 98%

Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation

Hall¹,

Grover²

1990

Handbook of Experimental Pharmacology

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“…The contribution of 3-OHBaP to the mutagenicity and carcinogenicity of BaP is generally thought to be small [25][26][27]. 3-OHBaP is a relatively weak mutagen and carcinogen, and forms smaller amounts of DNA adducts than more potent carcinogens such as BaP-7,8-dihydrodiol-9,10-oxide [28].…”

Section: Introductionmentioning

confidence: 99%

Binding of 3‐hydroxybenzo[a]pyrene to bovine hemoglobin and albumin

Sugihara

James

2003

J Biochem & Molecular Tox

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Previous studies examined the bioavailability and first-pass biotransformation of 3-hydroxy[(3)H]benzo[a]pyrene ([(3)H]-3-OHBaP) in an isolated perfused catfish intestinal model. This work showed that 3-OHBaP, or a metabolite formed in intestine, bound covalently to blood protein. In this study, the blood adducts were characterized in vitro by incubating bovine ferric hemoglobin or albumin with [(3)H]-3OHBaP under various conditions. Incubation of 2 microM [(3)H]-3-OHBaP with hemoglobin for 1 h resulted in 7.49 pmol bound/mg protein, while albumin binding was 1.37 pmol/mg protein. Mild acid hydrolysis released only 5% of the radioactivity from 3-OHBaP-hemoglobin adducts. After gel filtration, the 3-OHBaP-hemoglobin adducts were examined by HPLC analysis. A single peak of radioactivity was detected at the same retention time as the heme component of hemoglobin. Unbound 3-OHBaP was oxidized to BaP-3,6-dione during incubation with ferric hemoglobin. Treatment of hemoglobin with ascorbic acid decreased the formation of hemoglobin adducts by 33%, while hydrogen peroxide treatment increased adduct formation by 44%. Incubation of [(3)H]-BaP-3-beta-D-glucuronide (BaP-3G) with hemoglobin and beta-glucuronidase resulted in greater binding to hemoglobin than incubation with [(3)H]-3-OHBaP alone. The hemoglobin adduct obtained from [(3)H]-BaP-3G also co-migrated with heme. These results indicate that an oxidative process is involved in formation of the heme adduct and that 3-OHBaP or BaP-3G might be a precursor of the bound metabolite.

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“…benzo(a)pyrcne (9-OH-BP) (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). So far, The polycyclic aromatic hydrocarbon however, only the former has been implicated in carcinogenesis (15118).…”

Section: Introductionmentioning

confidence: 99%

“…Of these, the (+)-anti-trans-7,8-dihy-droxY-7,8-dihYdrobenZO(a)PYrene-g,~o-~POXide ( B P W is by far the most active and is considered to be the ultimate carcinogenic form of BP (19,20). Available evidence suggests that DNA binding from 9-OH-BP Proceeds via formation of a 9-OH-BP-4,5-epoxide intermediate (7,8,10,14,21). Quantitatively, the major binding site for anti-BPDE and, in particular, its (+)-enantiomer, is the 2-amino group Of guanine, Lvhich preferentially reacts with BPDE through its C-10 position (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

“…Modified DNA, native or heat denatured, was subjected to static fluorescence analysis and fluorescence decay measurements. The results were compared to those obtained with suitable model substances, 7,8,9,10-tetrahydroxy-7,8,9,10t e t rahydro b'e n zo (a) p y r e n e (B P- 7,8,9,10 t et ra 01) 4,5,9t r i h y d ro x y-4,5d i h y d robenzo(a)pyrene (9-OH-BP-4,5-diol) in solvents of different polarities. In addition, we have measured the fluorescence depolarization of modified DNA at different temperatures.…”

Section: Introductionmentioning

confidence: 99%

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Fluorescence Measurements of DNA-bound Metabolites of Benzo(a)pyrene Derivatives with Different Carcinogenic Effects

et al. 1984

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f)-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene (9-OH-BP) were metabolized by rat liver microsomes in the presence of calf thymus DNA, resulting in preferential DNA binding of fluorescent (+)-anti-BP-7,8-diol-9,lO-epoxide (BPDE) and 9-OH-BP-4,5-epoxide, respectively. When the DNA is denatured the fluorescence intensities of the bound metabolites change in a characteristic manner. Fluorescence decay measurements show that the intensity changes are due to changes in lifetimes of the excited states. Model substances for the bound metabolites were studied in solvents of different polarity. We found that the fluorescence changes observed after denaturation of the DNA may be explained as solvent polarity effects, so that denaturation forces the bound metabolites from a more hydrophobic environment to a hydrophilic one. Fluorescence depolarization studies as a function of temperature in combination with previous linear dichroism studies show that both BPDE and 9-0H-BP-4,S-epoxide form rigidly associated complexes with native DNA.

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Formation of DAN-binding products from isolated benzo[a]pyrene metabolites in rat liver nuclei

Cited by 30 publications

References 24 publications

Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation

Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation

Binding of 3‐hydroxybenzo[a]pyrene to bovine hemoglobin and albumin

Fluorescence Measurements of DNA-bound Metabolites of Benzo(a)pyrene Derivatives with Different Carcinogenic Effects

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