Assessment of the Tumor-Initiating Potential of α,β-Unsaturated Carbonyl Compounds by 32P Postlabeling Quantification of DNA Adducts In Vivo

Eder, Erwin; Budiawan,; Schüler, Dirk; Otteneder, Michael B.

doi:10.1007/978-3-642-60393-8_5

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…In subsequent computations, we have considered crotonaldehyde and R-chloroacrolein as examples of substituted acrolein-guanine adducts from two important groups of R,β-unsaturated carbonyl compounds. Crotonaldehyde is a member of the group of β-alkylacroleins, many of which have been found to be mutagenic and genotoxic (4,5,15,30,(32)(33)(34)(35)(36)(37)(38)(39)54). R-Chloroacrolein is a member of the family of R-haloacroleins, which are highly mutagenic (5,11,12,(51)(52)(53)(54).…”

Section: Methodsmentioning

confidence: 99%

“…Crotonaldehyde is a common β-methylacrolein derivative which, like other β-alkylated acroleins, has demonstrated mutagenic and genotoxic activities ( 4 , 5 , 15 , 30 , 32 , − . Furthermore, cancer induction has been linked to crotonaldehyde and other β-alkylated acroleins ( 26−28 , − . Similar properties have been found for alkylation at the carbonyl, e.g., methyl vinyl ketone and ethyl vinyl ketone ( 5 , 18 , 31 , 40 , 41 ).…”

Section: Introductionmentioning

confidence: 99%

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Structures of Acrolein−Guanine Adducts: A Semi-Empirical Self-Consistent Field and Nuclear Magnetic Resonance Spectral Study

Boerth

Eder

Hussain

et al. 1998

Chem. Res. Toxicol.

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The structures and conformations of adducts formed by reaction of guanosine with several mutagenic alpha,beta-unsaturated carbonyl compounds have been investigated by semi-empirical molecular orbital calculations and compared with NMR spectral results. Two cyclization processes taking place on the pyrimidine ring of guanine leading to two sets of regioisomers, 11-hydroxy- and 13-hydroxytetrahydropyrimidinoguanines (THPG), were considered. Relative stabilities and geometries of all configurations and conformations of adducts with acrolein, crotonaldehyde, and alpha-chloroacrolein were calculated by PM3, AM1, and MNDO methods. PM3 results were the most compatible with experimental structures based on 400-MHz 1H NMR spectroscopy. The most stable structures for the 11-hydroxy and 13-hydroxy THPG isomers from acrolein are predicted to have chair-like structures for the tetrahydropyrimidine ring and axial hydroxyl groups, as suggested by the NMR spectra of the isolated adducts. Of the possible isomers from guanine and crotonaldehyde, cis-11-hydroxy-13-methyl THPG with methyl and hydroxyl groups axial is predicted to be the most stable. The only isolated adduct is the trans-13-hydroxy-11-methyl THPG with methyl shown to be equatorial and hydroxyl axial by 1H NMR. This is completely consistent with the geometry predicted by PM3 for the 13-hydroxy regioisomer of crotonaldehyde. In the case of adducts of alpha-chloroacrolein, one stereoisomer predominates for each of the two possible regioisomers. For the 12-chloro-11-hydroxy isomer, the cis configuration with chlorine axial and hydroxyl quasi-axial is calculated to have the most stable geometry. In contrast, the 1H NMR spectrum supports a trans diaxial orientation, although the cis computed structure could also be accommodated by the spectrum. The 12-chloro-13-hydroxy regioisomer is unambiguously assigned as trans diaxial by PM3 calculations and 1H NMR spectroscopy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structures of Acrolein−Guanine Adducts: A Semi-Empirical Self-Consistent Field and Nuclear Magnetic Resonance Spectral Study

Boerth

Eder

Hussain

et al. 1998

Chem. Res. Toxicol.

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“…Although the structures of adducts in most of the spots are unknown at this time, two of the adducts visible on the autoradiograms could be identified due to previous experience with these particular adducts. These two spots correspond to deoxyguanosine adducts formed with HX and 4-hydroxynonenal (HNE) previously identified in 32 P postlabeling studies , . Both HX, HNE, and related compounds are products of lipid peroxidation via cyclooxygenases (COXs) or lipoxygenases (LOXs) − .…”

Section: Resultsmentioning

confidence: 69%

“…The natural outcome is that normal base pairing is prevented with concomitant misreading of the genetic code during transcription, leading to base transversions, lesions, DNA strand breaks, deletions, and frameshift mutation. This mechanism has been well-documented in animal systems and is believed to play a key role in human carcinogenesis ,− .…”

Section: Introductionmentioning

confidence: 99%

DNA Adducts as Biomarkers for Oxidative and Genotoxic Stress from Pesticides in Crop Plants

Boerth

Eder

Stanks

et al. 2008

J. Agric. Food Chem.

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Plant studies have been carried out to identify the nature and extent of the formation of adducts with DNA bases when treated with pesticide formulations. DNA extracted from crop plants after treatment with pesticide formulations has yielded evidence of adduct formation. The extent of DNA modification has been established by (32)P postlabeling studies. The radiochromatograms from (32)P postlabeling of isolated plant DNA from grapes, bush beans, soybeans, pumpkins, and cucumbers show elevated adduct levels in treated vegetable plants as compared with untreated controls. A number of different adduct spots appear, likely indicating adduct formation with pesticide molecules or their metabolites. The DNA adducts from hexenal and 4-hydroxy-2-nonenal were clearly observed, indicating oxidative stress and lipid peroxidation in the plant.

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The influence of the solvents DMSO and ethanol on the genotoxicity of α,β-unsaturated aldehydes in the SOS chromotest

Eder¹,

Deininger²

2002

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Assessment of the Tumor-Initiating Potential of α,β-Unsaturated Carbonyl Compounds by 32P Postlabeling Quantification of DNA Adducts In Vivo

Cited by 3 publications

References 16 publications

Structures of Acrolein−Guanine Adducts: A Semi-Empirical Self-Consistent Field and Nuclear Magnetic Resonance Spectral Study

Structures of Acrolein−Guanine Adducts: A Semi-Empirical Self-Consistent Field and Nuclear Magnetic Resonance Spectral Study

DNA Adducts as Biomarkers for Oxidative and Genotoxic Stress from Pesticides in Crop Plants

The influence of the solvents DMSO and ethanol on the genotoxicity of α,β-unsaturated aldehydes in the SOS chromotest

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