Effects of acrolein on DNA synthesis <i>in vitro</i>

Munsch, Nicole; Recondo, Anne-Marie de; Frayssinet, C

doi:10.1016/0014-5793(73)80671-4

Cited by 24 publications

(3 citation statements)

References 7 publications

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“…,/3-Unsaturated aldehydes have been reported to exhibit a variety of biological activities (28). It has been suggested that the activity of ,/3-unsaturated aldehydes may involve reaction with critical cellular sulfhydryls (29- 21). Toxicity of aldehydes has been correlated with reactivity toward thiols (22).…”

Section: Resultsmentioning

confidence: 99%

Reaction of (E,E)-muconaldehyde and its aldehydic metabolites, (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxyhexa-2,4-dienal, with glutathione

Kline¹,

Xiang²,

Goldstein³

et al. 1993

Chem. Res. Toxicol.

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(E,E)-Muconaldehyde (muconaldehyde) has been identified as a hematotoxic metabolite of benzene in vitro. It is metabolized in mouse liver cytosol to oxidized and reduced derivatives including the alpha, beta-unsaturated aldehydes (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxy-2,4-hexadienal. In this study we have synthesized the aldehydic metabolites of muconaldehyde. The reaction of glutathione with muconaldehyde and its aldehyde metabolites was investigated. Reactions were bimolecular and stoichiometric in aldehyde and glutathione in the initial phases. Second-order rate constants were determined, and the rates were in the order muconaldehyde > (E,E)-6-hydroxy-2,4-hexadienal > (E,E)-6-oxohexadienoic acid. Further investigation of the reaction of muconaldehyde with glutathione showed that the bimolecular reaction is reversible but the initial product decomposed irreversibly to two or more products, one of which had a red-shifted UV spectrum. Rate constants for these subsequent reactions were determined. The results are discussed in terms of the toxicity of muconaldehyde at tissues distal from the liver, where it is believed to be formed from the metabolism of benzene.

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Section: Resultsmentioning

confidence: 99%

Reaction of (E,E)-muconaldehyde and its aldehydic metabolites, (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxyhexa-2,4-dienal, with glutathione

Kline¹,

Xiang²,

Goldstein³

et al. 1993

Chem. Res. Toxicol.

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“…The toxicity of the highly active aldehydes can be associated with inhibition of the mitochondrial oxidative metabolism, previously illustrated for short chain aldehydes (Schauenstein et al, 1977), and also with the fact that these compounds, notably a,/3-unsaturated aldehydes, can combine with biochemical nucleophiles such as sulfhydryl, amino and hydroxy groups. Thus, acrolein has been shown to inhibit DNA-polymerase (Munch et al, 1973).…”

Section: Mean Activity Values For 12 Groups Of Compounds In Four Testmentioning

confidence: 99%

An evaluation of the utility of four in vitro short term tests for predicting the cytotoxicity of individual compounds derived from tobacco smoke

Curvall¹,

Enzell²,

Pettersson

1984

Cell Biol Toxicol

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An evaluation of results obtained earlier and now complemented to provide information on the activity of 305 compounds in four in vitro tests has been undertaken. Biological data based on the effects of these compounds on cell multiplication, oxidative metabolism, ciliary activity and membrane permeability are compared with a view to clarifying intersystem similarities and differences and, on the basis of a mean activity parameter, evaluating structure-activity and functionality-activity relationships. High mean activity is observed for 59 compounds, of which 18 are phenols, 14 aldehydes, 8 N-heterocyclics, 7 alcohols and 5 hydrocarbons. The medium and low mean activity groups comprise 105 and 131 members, respectively, and both include representatives of all functionalities examined. Delineation of the 305 compounds using 45 descriptors, and computer-assisted matching of these and any combination of them against the mean activity showed the most toxic single descriptor group to be terpenoids followed by indoles and naphthalenes, and the most toxic two-descriptor group to be alpha,beta-unsaturated carbonyls followed by n-alkyl alcohols, aldehydes and acids. Examination of intersystem similarities and differences, using a high-medium-low scale, shows that all four systems give the same result for 35 percent of the compounds, three systems for 41 to 48 percent of the compounds, and two systems for 53 and 64 percent of the compounds. Of all compounds, 16 percent exhibit a high activity in one system and a low activity in the other three, or vice versa. Nearly half of these discrepancies are caused by the membrane permeability system showing diverging results, while none of them are related to the brown fat cell system. The last test system is found to best represent the mean activity obtained from the four systems and the one of choice if reducing the number of tests from four to one.

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“…Its high reactivity makes acrolein a dangerous substance for the living cell, whose nucleus (Moule and Frayssinet, 1971;Alarcon, 1972) and locomotor apparatus (Wynder et al, 1965;Battista and Kensler 1970;Munsch et al, 1973) (Izard, 1967(Izard, , 1973Brown and Fowler, 1967;Andersen et al, 1972;Izard and Liberman, 1978).…”

Section: Introductionmentioning

confidence: 99%