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E Eder

Publications and source records attributed to E Eder.

At least 55 records · Page 3Linked to original sources
PubMed1991

Mutagenicity of 2-methylacrolein, 2-ethylacrolein and 2-propylacrolein in Salmonella typhimurium TA100. A comparative study.

The C2-alkylated acrolein derivatives 2-methylacrolein, 2-ethylacrolein and 2-propylacrolein are mutagenic in Salmonella typhimurium TA100. They are direct mutagens, their mutagenic potency being inversely proportional to the size of the alkylating substituent in the C2 position. In the presence of S9 mix, the mutagenicity of all these substances is considerably reduced; the reduction in mutagenicity is inversely proportional to the direct mutagenic potential of the substance. As shown for 2-methylacrolein, the reduction in mutagenicity is dependent on the concentration of S9 in the S9 mix and is not significantly influenced by heat inactivation of the S9 mix or by addition of TCPO, an inhibitor of epoxide hydrolase, to the testing system. There are no indications of enzymatic activation by the metabolizing microsomal system.

Acrolein↗
PubMed1991

Genotoxicity of p-nitrocinnamaldehyde and related alpha, beta-unsaturated carbonyl compounds in two bacterial assays.

Seventeen cinnamaldehydes, cinnamic acids, 2-furylacroleins and related compounds were tested in the Salmonella preincubation reversion assay and in the SOS chromotest. Of eight compounds containing nitrogroups, seven were clearly mutagenic in the presence of S9 mix and six in its absence; whereas none of the parent compounds not containing a nitrogroup and none of the congeners containing chlorine, methoxy or amino groups were mutagenic. Metabolic epoxidation was excluded in additional experiments using SKF525, an inhibitor of mono-oxygenases, and trichloropropene oxide, an inhibitor of epoxide hydrolases. Less or no mutagenicity was found in the nitroreductase deficient strains Salmonella typhimurium TA100NR or TA98NR and in the O-acetyltransferase deficient strains TA100/1,8-DNP6 or TA98/1,8-DNP6 except with 5-nitro-2-furylacrolein which exhibited decreased mutagenicity in TA100NR when compared with TA100 but the highest mutagenicity in TA100/1,8-DNP6. Less or no genotoxic activity was found in the SOS chromotest when using the nitroreductase deficient Escherichia coli strain PQ253 whereas all seven compounds tested were positive in strain PQ37. The results demonstrate the importance of the nitro group and that the compounds are activated either by bacterial nitroreductase or by the nitroreductase in the S9 mix. A chemical activation of the acrolein moiety by the negative inductive effect of the nitro group is unlikely. The genotoxicity of the cinnamyl compounds is dependent on the position of the nitro group in the phenyl ring. The genotoxicities of the p-nitro compounds were about two orders of magnitude higher than those of the ortho and meta congeners. The comparison between the Ames test and the SOS chromotest showed good agreement.

Acrolein↗
PubMed1990

Mutagenicity and genotoxicity of ethylvinyl ketone in bacterial tests.

The mutagenic and genotoxic effects of ethylvinyl ketone were investigated. This alpha, beta-unsaturated carbonyl compound is widely distributed in the environment, in particular in food. Whereas ethylvinyl ketone shows only weak genotoxicity in the SOS Chromotest with Escherichia coli PQ37, it was distinctly mutagenic per se in the Salmonella preincubation assay with TA100. Using SKF 525 (an inhibitor of microsomal monooxygenase) and trichloropropene oxide (an inhibitor of epoxide hydrolase) we found indication for additional activation via epoxidation by S9 mix. The need for further investigation of the genotoxic, mutagenic and carcinogenic effects of this compound is strongly indicated.

Animals↗
PubMed1990

Molecular mechanisms of DNA damage initiated by alpha, beta-unsaturated carbonyl compounds as criteria for genotoxicity and mutagenicity.

alpha, beta-Unsaturated carbonyl compounds are important not only from a theoretical but also a practical standpoint. These ubiquitous compounds can interact with DNA through various mechanisms. The predominant interaction is the formation of cyclic 1,N2-deoxyguanosine adducts; 7,8-cyclic guanine adducts are also found. We have synthesized and characterized the stereoisomers of adducts formed by about 20 alpha, beta-unsaturated carbonyl compounds. The different types of adducts and the mutagenic and genotoxic response can be explained by the molecular structures of the agents. Compounds forming saturated cyclic adducts are mutagenic in S. typhimurium strain TA100 and to a lesser extent in TA1535. Substances with a leaving group at the C-3 position form unsaturated conjugated cyclic adducts and are mutagenic only in the His D3052 frameshift strains with an intact excision repair system (no urvA mutation). Metabolic epoxidation of the double bond and other metabolic activation, e.g., activation of the nitrogroups via nitroreductases, were also found to contribute to genotoxic and mutagenic activities. Our results have further elucidated the genotoxic mechanisms of these compounds; however, additional investigations are required for a complete understanding of the genotoxic activity of this class of compounds.

Acrolein↗
PubMed1989

Crotonaldehyde is mutagenic in Salmonella typhimurium TA100.

The mutagenicity of crotonaldehyde in Salmonella typhimurium TA100 cannot be demonstrated in the standard plate incorporation assay. However, as reported earlier by our group, this alpha, beta-unsaturated aldehyde is clearly mutagenic in the liquid assay modification of this testing procedure. Carried out because of the doubts recently expressed by Cooper et al. (Environ Mutagen 9:289-295, 1987) concerning the observed mutagenicity of crotonaldehyde in S. typhimurium TA100, this study confirms that this compound is clearly a direct (without activation by mammalian microsomes)-acting mutagen in S. typhimurium TA100 under appropriate conditions in the preincubation assay. The observed mutagenicity is increased by extended preincubation time and increased bacterial cell densities.

Aldehydes↗
PubMed1989

The dependence of the mutagenicity of methanesulphonic acid esters in S. typhimurium TA100 on the alkylation mechanism.

Four different model nucleophiles, 4-(p-nitrobenzyl)pyridine (NBP), N-methylmercaptoimidazole (MMI), trifluoroacetic acid (TFA) and H2O were tested with 22 methanesulphonates of widely varying structures for their suitability to predict mutagenic activities in S. typhimurium TA100. The soft nucleophiles NBP (N-alkylation) and MMI (S-alkylation) revealed as highly sensitive for SN2 reactivities whereas TFA (solvolysis at the O-atom) and H2O (hydrolysis) were very sensitive for SN1 reactivities. No correlation between the NBP or the MMI test and the Ames test was found. Quite good correlations could be demonstrated for the TFA test and the hydrolysis rates: with rising activities in the TFA solvolysis the mutagenic potencies were increasing up to a maximum at i-propyl methanesulphonate. After that due to the fast hydrolysis the mutagenicities were decreasing again despite increasing TFA solvolysis rates. In general the secondary methanesulphonates exerted high SN1 reactivities and distinct mutagenic activities, whereas the primary compounds showed no or very low SN1 reactivities and low mutagenic potentials. The "activated" compounds cyclopropylmethyl methanesulphonate, benzyl methanesulphonate and allyl methanesulphonate exerted high SN1 and SN2 reactivities. Methyl methanesulphonate displayed a high mutagenicity in spite of its lack in SN1 reactivity. This is probably due to the induction of the error prone repair (pkM 101 plasmid in TA100). The relation between the alkylating reactivities (SN1 and SN2) and the molecular mechanisms leading to back mutation is discussed.

Alkylating Agents↗
PubMed1989

Genotoxicity of monofunctional methanesulphonates in the SOS chromotest as a function of alkylation mechanisms. A comparison with the mutagenicity in S. typhimurium TA100.

17 monofunctional methanesulphonates of widely varying structures were investigated in the SOS chromotest using the E. coli strain PQ37. All compounds tested were positive in this assay. The monofunctional methanesulphonates in general possess low SOSiP values. Five of the compounds tested i.e. iBMS, NpMS, 2 PhPMS, PkMS and 1,3-DC12PMS (for abbreviations see Table 1) did not show increasing beta-galactosidase activity and both the positive induction factors and the positive SOSiP values resulted from the toxicity correction as performed according to Quillardet and Hofnung (1985). In general methanesulphonates with a higher SN1 reactivity, in particular the secondary compounds, showed clear genotoxic activities whereas those possessing low SN1 reactivities (primary compounds) induced a low SOS repair indicating that the alkylation of O-atoms in the DNA bases contributes more to the induction of SOS repair in strain PQ37 than N-alkylations. The only exception was methyl methanesulphonate (MMS) which possessed a very high SN2 reactivity but a rather low SN1 reactivity. It had the highest SOSiP value of all tested methanesulphonates. No dependence of the genotoxicity on the SN2 reactivity could be found in this series. In general the phenyl-substituted methanesulphonates showed higher SOSiP values, which is presumably due to their relatively high SN1 reactivities and their relatively long life times in aqueous systems. There is a clear relationship between SN1 reactivities and the SOSiP values: the SOSiP values increase with rising SN1 reactivities reaching a maximum at iPMS after which the genotoxicities decrease due to the decreasing life times. The compounds with very high SN1 reactivities also possess very high hydrolysis rates. A good correlation could be established between the mutagenicities in S. typhimurium TA100 and the SOS chromotest (strain PQ37). Only 4 small deviations from this correlation could be found. The reasons for these deviations are discussed.

Alkylation↗
PubMed1989

Methyl methanesulphonate (MMS) is clearly mutagenic in S. typhimurium strain TA1535; a comparison with strain TA100.

No mutagenicity or an uncertain mutagenic response has been reported in the literature for methyl methanesulphonate (MMS) in S. typhimurium strain TA1535 when using the plate assay. In our studies we found a reproducible mutagenic activity of 62 revertants/mumole and plate for MMS in strain TA1535 when using the preincubation assay. A dose-dependent increase in revertants was, however, observed only at fairly high doses (exceeding 4 mumole). Two different slopes were observed in the dose-response curve when testing MMS with strain TA100. Slope A is dependent on the error-prone response, possible only in strain TA100 due to the pKm101 plasmid (R factor) but not possible in strain TA1535 due to its umuDC deficiency. Slope B observed at higher doses (as in strain TA1535) could be explained through a GC----AT transition initiated by the O6-methylation of guanine. Our findings demonstrate that MMS induces back mutation in S. typhimurium strains carrying the hisG46 missense mutation due to the formation of O6-methylguanine. In the case of strain TA100 the pKm101 plasmid-mediated error-prone mechanism is, however, the predominant process in MMS mutagenesis which leads to a higher mutagenic response at much lower doses than the GT----AT transition in strain TA1535.

DNA, Bacterial↗
PubMed1989

Induction of sfiA SOS function by peroxides using three different E. coli strains.

Five peroxides and two related compounds were tested for genotoxicity by the SOS Chromotest using 3 different E. coli strains (PQ37, PM21, GC4798). All tested hydroperoxides (hydrogen peroxide, tert-butylhydroperoxide, cumene hydroperoxide) were clearly positive in all strains. From a comparison of results obtained from the different strains it can be concluded that neither DNA lesions leading to the induction of excision repair nor covalent binding of radicals to DNA is responsible for the induction of sfiA-SOS function by hydroperoxides. Among the remaining compounds tested, only dibenzoylperoxide gave a clearly positive result in strain PQ37 whereas di-tert-butylperoxide and azobisisobutyronitrile showed only borderline activity. When using strains PM21 and GC4798, none of the latter compounds was positive. Paraquat was inactive in all strains.

DNA↗
PubMed1989

Induction of SOS repair by monofunctional methanesulphonates in various Escherichia coli strains. Structure-activity relationships in comparison with mutagenicity in Salmonella typhimurium.

Seventeen monofunctional alkylmethanesulphonates of widely varying structures were investigated in the SOS Chromotest using the Escherichia coli strains PM21, PQ37 and GC4798. As a measure of the SOS-inducing activity, the beta-galactosidase enzyme units (Up/mumol) were determined. Strains PM21 and PQ37 gave similar results in spite of the presence of different genetic markers. In general, the SN1 type secondary compounds (O-alkylation) induced higher SOS repair than the SN2 type primary compounds (N-alkylation). However, methylmethanesulphonate exerted the highest SOS induction of all tested strains, presumably due to its extremely high SN2 reactivity. In general, strain GC4798, which lacks 3-alkyladenine-DNA glycosylases I and II, was more sensitive towards monofunctional alkylating compounds and in particular towards the SN2 type compounds. A good correlation was found between the SOS repair response in the E. coli strains PM21 and PQ37 and the mutagenicity in Salmonella typhimurium TA100. There was, however, little correspondence when comparing the two measures used for the SOS-inducing activity in this work, the SOSIP (SOS-inducing potency) and the specific beta-galactosidase activity (Up/mumol). This effect was explained by the different toxicity corrections used for the calculation of the two measures. Whereas for the SOSIP value the single constitutive enzyme alkaline phosphatase is used, for the Up/mumol the absorbance at 600 nm, which indicates the growth delay (overall toxicity), is utilized. The influence of the toxicity corrections is discussed in more detail.

Alkylating Agents↗
PubMed1989

[The free TRAM (transverse rectus abdominis myocutaneous) flap--a new possibility in breast reconstruction].

Free TRAM slap transfer for breast reconstruction following mastectomy is a functional operation requiring knowledge of aesthetic surgery and mastering of microsurgical techniques. It overcomes the shortcomings of the pedicled TRAM (transverse rectus abdominis myocutaneous flap. By taking advantage of the dominant vascular pedicle (deep inferior epigastric artery and vein) it provides a better vascularization even in zones 3 and 4 and allows a greater freedom in tailoring of the flap. The vascular pedicle is anastomosed to the vessels in axilla providing high filling pressure. Both facts allow the use of free TRAM flap even after irradiation or radical mastectomy. A secondary operation, the "mammilla-areola complex" reconstruction and contralateral breast surgery to achieve symmetry, follow after 3-4 months. Clinical application in 6 post-mastectomy patients is discussed as well as the operative technique of free TRAM flap.

Adult↗
PubMed1988

Breast reconstruction by the free lower transverse rectus abdominis musculocutaneous flap.

Free TRAM flap transfer for breast reconstruction following mastectomy overcomes the shortcomings of the pedicled TRAM flap. It ensures the perfusion of the entire flap via its dominant vascular pedicle and allows for flexibility in the design of the ensuing breast mound. The authors' experience with ten free lower TRAM flap transfers is reviewed. The present surgical technique is described and three cases are presented to illustrate its application. The advantages and limitations of the method are compared particularly with its pedicled version.

Abdominal Muscles↗
PubMed1987

The role of biotransformation in the genotoxicity of allylic compounds.

Allylic compounds exert direct genotoxic activities which depend on the chemical nature of the leaving group and on further substituents. Besides the direct genotoxic effects, metabolic activation mechanisms are also conceivable. Epoxidation seems to play a minor role in bioactivation, whereas the metabolic formation of strongly mutagenic alpha, beta-unsaturated carbonyl compounds is obviously of great importance for the indirect genotoxicity of allylic compounds. Only in the case of 2,3-dichloro-1-propene is an epoxide formed which is extremely unstable and immediately rearranges to the strong mutagen, 1,3-dichloroacetone.

Allyl Compounds↗
PubMed1987

Allylic compounds bind directly to DNA: investigation of the binding mechanisms in vitro.

The in vitro binding of three allyl compounds, allyl methanesulphonate, allyl bromide and allyl chloride to DNA from salmon sperm was investigated. Kinetic DNA-alkylation measurements revealed significant differences between the strongly alkylating allyl methanesulphonate and allyl bromide with half-life values of 1.5 h and 8.1 h, respectively and the weakly alkylating allyl chloride with a half-life value of 360 h. Five alkylated nucleic bases, 3-allyladenine, N6-allyladenine, N2-allylguanine, 7-allylguanine and O6-allylguanine, could be identified after DNA-alkylation with all three allyl compounds.

Alkylating Agents↗
PubMed1986

Mutagenicity of chloroolefins in the Salmonella/mammalian microsome test--II. Structural requirements for the metabolic activation of non-allylic chloropropenes and methylated derivatives via epoxide formation.

Non-allylic chloropropenes and their methyl-homologues, being chloro-substituted exclusively in vinylic position, are mutagenic in the presence of metabolizing rat liver homogenate fraction (S9 mix). This can be interpreted as the result of polarizing inductive (I-) and mesomeric (M-) effects exerted by Cl- as well as by CH3-substituents on the olefinic double bond. The extent of their mutagenic activity increases with longer preincubation time and/or a higher concentration of rat liver homogenate fraction (S9) in the S9 mix. The only exception from this rule of a qualitative correlation of C = C-bond polarization due to asymmetric substitution and mutagenic activity is 1-chloro-2-methyl-1-propene which is non-mutagenic. In this case effects of a steric hindrance of two voluminous CH3-substituents attached to one C-atom of the C = C-bond might inhibit enzymatic attack of the double bond by microsomal oxygenase. Mutagenic activity is invariably decreased in the presence of SKF525, inhibitor of microsomal oxygenase, and increased when 1,1,1-trichloropropene-2,3-oxide (TCPO), inhibitor of epoxide hydrolase, is added to the test system. This is a strong argument for metabolic activation of these substances occurring via epoxide formation.

Alkenes↗
PubMed1986

Structure-activity relationships of alpha, beta-unsaturated carbonylic compounds.

The mutagenicity and probably the carcinogenicity of alpha, beta-unsaturated carbonylic compounds such as acrolein are based on direct genotoxic interaction with nucleic acid bases via Michael addition or Schiff's base formation. Alkyl and aryl substitution at the alpha and beta carbon atoms reduces or abolishes the mutagenic potential whereas halogen substitution in either position increases mutagenicity. These structure-activity relationships can be predicted from theoretical considerations of well-known electron shift mechanisms. The formation of alpha, beta-unsaturated carbonyls from allylic halides (or similar types of compounds with appropriate leaving groups) has been experimentally demonstrated with appropriate metabolites of allyl bromide in in rats.

Acrolein↗