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Biomedical subjects

C Hoffman

Publications and source records attributed to C Hoffman.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Genotoxicity of allyl compounds--a quick screening strategy based on structure-activity relationships and a battery of prescreening tests.

A proposed strategy for the rapid screening of the genotoxic activities of allylic compounds is based on structure-activity relationships elaborated by a battery of quick screening tests. The procedure facilitates the selection of appropriate representatives of this class of compound for subsequent testing, so that both expensive and time-consuming assays and the use of animals can be drastically reduced. The studies have yielded several important results. Allylic compounds with suitable leaving groups have been shown to exert direct genotoxic activity. In the metabolic activation of these compounds the formation of epoxides is clearly of minor importance, playing a role only in the case of 2,3-dichloro-1-propene and some of its homologues, whereas all reactive allylic compounds can be activated to genotoxic alpha,beta-unsaturated carbonyl compounds (acrolein). The most significant factors for genotoxicity are the leaving groups and halogen substituents. Alkyl substituents increase the direct genotoxicity while decreasing the indirect activity (via acroleins).

Allyl Compounds↗
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

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

H-reflex recovery curve in syringomyelia.

H-reflex recovery curves were obtained from 13 patients with cervical syringomyelia to assess motor neurone excitability, and results were compared with control subjects and patients with spasticity due to stroke. The median nerve was stimulated at the elbow and the H-reflex was recorded from the flexor carpi radialis muscle. Double pulses with interstimulus intervals ranging from 75 to 900 ms were delivered. The H-reflex was unobtainable from either limb in two patients with advanced disease and loss of all sensory modalities. H-reflex recovery curves from syrinx patients showed marked facilitation with interstimulus intervals ranging from 150 to 300 ms. Facilitation was higher than in patients with spasticity due to stroke. Results are indicative of an increased motor neurone excitability in patients with cervical syringomyelia.

Adolescent↗