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E Eder

Publications and source records attributed to E Eder.

78 records · Page 5Linked to original sources
PubMedDate not supplied

Identification and characterization of deoxyguanosine adducts of methyl vinyl ketone and ethyl vinyl ketone. Genotoxicity of the ketones in the SOS Chromotest.

The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structures elucidated: the cyclic 1,N2 adducts, the linear N7 adducts with one still-unreacted carbonyl function, and the cyclic 1,N2, linear N7, bis adducts. The spectroscopic and other relevant characterization data for the deoxyguanosine adducts and the corresponding guanine adducts are presented here together with details of the chromatographic methods used for isolation. The adducts described could also be isolated in the reactions of MVK and EVK with 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated either with nucleosides other than deoxyguanosine or with nucleotides other than 2'-deoxyguanosine 5'-monophosphate, indicating that the guanine moiety is the most reactive DNA constituent for MVK and EVK. MVK and EVK were clearly genotoxic in the SOS Chromotest according to the criteria of Quillardet and Hofnung. The formation of these adducts was proposed as the mechanism for the genotoxicity of MVK and EVK: all data available support the assumption that MVK and EVK represent a mutagenic and carcinogenic risk for mankind.

Butanones↗
PubMedDate not supplied

Theoretical structure-activity study of mutagenic allyl chlorides.

Ab initio molecular orbital calculations at the STO-3G and 3-21G levels were used to clarify the mechanism of mutagenic action of various substituted allyl chlorides. Computed molecular properties were compared with experimental mutagenic potentials of these allylic compounds. In agreement with experiment, the computational results suggest that the primary mechanism of action involves the SN1 formation of allylic cations which then react with nucleophilic centers of nucleic acid bases. The usefulness of computed properties in estimating the degree of alkylating activity and mutagenicity was evaluated. In general, stability of the allylic carbocation intermediate and the degree of charge delocalization in the allyl system correlate well with observed mutagenic potentials.

Alkylation↗
PubMedDate not supplied

Identification and characterization of deoxyguanosine-crotonaldehyde adducts. Formation of 7,8 cyclic adducts and 1,N2,7,8 bis-cyclic adducts.

Crotonaldehyde, a chemically reactive alpha,beta-unsaturated carbonyl compound, is an important industrial chemical and a ubiquitous environmental pollutant. It has been shown to be carcinogenic and mutagenic. We have studied the reaction of crotonaldehyde with nucleosides and 5'-mononucleotides and found three different types of adducts with deoxyguanosine and 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated either with nucleosides other than deoxyguanosine or with nucleotides other than 2'-deoxyguanosine 5'-monophosphate. With crotonaldehyde, deoxyguanosine produced 1,N2 and 7,8 adducts as well as 1,N2/7,8 bis-adducts. The 1,N2 adducts were mixtures of diastereomers: one pair in which the substituents in the newly formed ring were trans [adduct Ia (6S,8S) and (6R,8R)], about 94%, and another pair Ib in which they were cis. In the case of the 7,8-adducts IIa,b, the ribose was cleaved and a mixture of isomers in which the substituents were cis-IIa and trans-IIb (2:1) in the newly formed tetrahydropyrrole ring was observed. A 3:2 cis-IIIa and trans-IIIb mixture of 1,N2,7,8 bis-adducts was found with the isomerism in the newly formed tetrahydropyrrole ring in analogy to the 7,8 adducts IIa,b. The corresponding bis-adduct with the cis form in the newly formed tetrahydropyrimidine ring was not observed.

Aldehydes↗
PubMedDate not supplied

Identification and characterization of deoxyguanosine adducts of mutagenic beta-alkyl-substituted acrolein congeners.

The reaction of the mutagenic beta-alkyl-substituted acroleins (E)-2-pentenal, (E)-2-hexenal, (E,E)-2,4-hexadienal, and 3,3-dimethylacrolein with nucleosides and 5'-mononucleotides was studied. We found two different types of adducts with deoxyguanosine and 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated with either nucleosides other than deoxyguanosine or nucleotides other than 2'-deoxyguanosine 5'-monophosphate. With pentenal, hexenal, and 3,3-dimethylacrolein, we identified and characterized 1,N2-cyclic adducts and 7,8-cyclic adducts. The 1,N2-adducts of pentenal and hexenal were mixtures of diastereomers, one pair in which the substituents in the newly formed ring were trans (6S,8S and 6R,8R) and another in which they were cis. The cis isomers were formed to a much lesser extent. In all cases, the regioisomer is formed in which the OH group is vicinal to the N-1 atom of the guanine moiety. In the case of the 7,8 adducts, the ribose cleaved spontaneously during the reaction, and a mixture of isomers in which the substituents were cis and trans in the newly formed tetrahydropyrrole ring was observed. Since these compounds form adducts in a similar way to crotonaldehyde and are also mutagenic like crotonaldehyde, it was proposed to regard them as carcinogenic, like crotonaldehyde, unless experimental examination demonstrates nonmutagenicity.

Acrolein↗
PubMedDate not supplied

Metabolism of 2,3-dichloro-1-propene in the rat. Consideration of bioactivation mechanisms.

At the present time, comprehensive metabolism studies of 2,3-dichloro-1-propene (2,3-DCP) have not yet been reported. We have investigated the biotransformation of 2,3-DCP using female Wistar rats in order to elucidate the bioactivation mechanisms. 175 mg/kg, 1,3-14C-2,3-DCP in corn oil was administered to a rat. The animal was killed 20 hr later. Approximately 56.7% of the radioactivity was excreted in the urine, 1.6% in the feces, 5.3% was exhaled as unchanged 2,3-DCP, and 0.3% as CO2. 31.3% remained in the organs and the carcass. Three metabolic pathways were established. 1) Conjugation with GSH leading to S-(2-chloro-2-propenyl)mercapturic acid. 2) The P450 induced epoxidation with subsequent rearrangement to highly mutagenic 1,3-dichloroacetone. 1,3-Dichloroacetone was further converted to the dimercapturic acid, 1,3-(2-propanone)-bis-S-(N-acetylcysteine). 3) The hydrolysis to 2-chloroallyl alcohol followed by alcohol dehydrogenase catalyzed formation of highly mutagenic 2-chloroacrolein. The 2-chloroallyl alcohol is excreted directly in the urine and as the glucuronide. 2-Chloroacrolein is further oxidized to 2-chloroacrylic acid which is also excreted in the urine.

Allyl Compounds↗