Cytotoxicity, DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes
Mutation Research/Genetic ToxicologyPublished 1 August 1986
Giovanni Brambilla, Luigi Sciabà, Patrizia Faggin, A. Maura, Umberto M. Marinari, M. Ferro
Citations153
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Since 4-hydroxyalkenals have been shown to originate from biomembrane lipids peroxidation, these findings should be taken into consideration in the assessment of the genotoxic role of lipoperoxidation in humans.
Abstract
The cytotoxic and genotoxic activities of 4-hydroxypentenal (HPE), 4-hydroxyhexenal (HHE), 4-hydroxyoctenal (HOE), 4-hydroxynonenal (HNE) and 4-hydroxyundecenal (HUE) were investigated in Chinese hamster ovary (CHO) cells. All five 4-hydroxyalkenals reduced plating efficiency in a concentration (ranging from 7 to 170 microM) lower than that producing a parallel reduction of trypan blue-excluding cells, but with both methods the increase in molarity needed to obtain a lethal effect was constantly rather small. With all five 4-hydroxyalkenals a significant amount of DNA fragmentation, as revealed either by the alkaline elution assay or by alkaline denaturation followed by chromatographic partition of single- and double-stranded DNA, was detected only after cell exposure to a cytotoxic concentration. HPE, HHE and HOE induced a clear-cut increase of sister-chromatid exchange (SCE) frequency, while that displayed by cells treated with HNE and HUE was minimal, even if dose-dependent and statistically significant. Since 4-hydroxyalkenals have been shown to originate from biomembrane lipids peroxidation, these findings should be taken into consideration in the assessment of the genotoxic role of lipoperoxidation in humans.
Keywords
ChemistryMedicineBiochemistry, Genetics and Molecular Biology
NatureNew Giemsa method for the differential staining of sister chromatids
3,197 Citations1974Paul Perry, Sheldon Wolff
If human lymphocytes1 or Chinese hamster2 cells are treated with the base analogue 5-bromodeoxyuridine in the latter part of the S period, Giemsa stained chromosomes exhibit a pattern of condensed and extended segments along their length, allowing the identification of the two chromatids, and the observation of sister chromatid exchanges (SCEs) without recourse to autoradiography.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid MetabolismIdentification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids
1,091 Citations1980Angelo Benedetti, Mario Comporti +1 more
Investigations suggest that as compared to 4-hydroxynonenal very low amounts of other 4-Hydroxyalkenals are formed by actively peroxidizing liver microsomes, and this finding may help to elucidate the mechanism by which lipid peroxidation causes deleterious effects on cells and cell constituents.
BiochemistryFractionation of DNA from mammalian cells by alkaline elution
830 Citations1976Kurt W. Kohn, Leonard C. Erickson +2 more
The method of alkaline elution provides a sensitive measure of DNA single-strand length distribution in mamalian cells and is applicable to a variety of problems concerning DNA damage, repair, and replication.
Biochemical JournalSeparation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes
623 Citations1982H. Esterbauer, Kevin H. Cheeseman +3 more
It is concluded that considerable amounts of biologically reactive carbonyl derivatives are released in lipid peroxidation and yet may not be picked up by the thiobarbituric acid reaction.
Mutation Research/Fundamental and Molecular Mechanisms of MutagenesisNaturally occurring carbonyl compounds are mutagens Salmonella tester strain TA104
590 Citations1985Lawrence J. Marnett, Holly K. Hurd +4 more
Testing conducted with strains that carry the nonsense mutation in different repair backgrounds indicates that the presence of pKM101 and the deletion of the uvrB gene facilitate the detection of enals and dicarbonyls, but not malondialdehyde, as mutagens.
Mutation Research/Reviews in Genetic ToxicologySister-chromatid exchanges: A report of the GENE-TOX program
558 Citations1981Samuel A. Latt, James W. Allen +9 more
British Journal of CancerFree Radicals, Lipid Peroxidation and Cancer
514 Citations1982John T. Butler
This book records the proceedings of a symposium on cancer topics organized by the N.Hormone therapy, particularly as, by modern standards, it is relatively inexpensive and most of the proposed extrapolations are quite plausible.
Biochemical JournalSeparation and characterization of the aldehydic products of lipid peroxidation stimulated by carbon tetrachloride or ADP-iron in isolated rat hepatocytes and rat liver microsomal suspensions
363 Citations1985Giuseppe Poli, Umberto Dianzani +4 more
The stoichiometric evaluation of fatty acid loss and the production of malonaldehyde and other carbonyls suggests that the pathways of lipid peroxidation triggered by CCl4 and ADP-iron are different.
Biochemical JournalMetabolism of the lipid peroxidation product 4-hydroxynonenal by isolated hepatocytes and by liver cytosolic fractions
236 Citations1985H. Esterbauer, Helmward Zöllner +1 more
The effective conversion of the cytotoxic 4-hydroxynonenal and other reactive aldehydes to alcohols, which are probably less toxic, could play a role in the general defence system of the liver against toxic products arising from radical-induced lipid peroxidation.
PubMedDNA-protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells.
169 Citations1978Regina A. G. Ewig, Kurt W. Kohn
The possibility of discriminating these two classes of cross-links in L1210 cells treated with haloethylnitrosoureas or nitrogen mustard was explored with the alkaline elution technique, based on sensitivity to proteinase K; the proteinase-sensitiveCross-links appear to be DNA-protein cross- links, and the protein enzyme-resistant class may include interstrand cross- Links.
NatureAssociation of mammalian cell death with a specific endonucleolytic degradation of DNA
169 Citations1974Jerry R. Williams, John B. Little +1 more
Human and rodent cells treated with several diverse agents which cause cell death, had similar distinct patterns of DNA degradation as assayed by alkaline sucrose gradient techniques, suggesting this degradation may be a general mechanism concomitant with, if not a precedent of, mammalian cell death.
Journal of Lipid ResearchAutoxidation of polyunsaturated esters in water: chemical structure and biological activity of the products
148 Citations1967E. Schauenstein
Synthetic short-chain (C(4)-C(10)) hydroxylated alpha,-unsaturated aldehydes have been shown to have this action and also to cause morphological changes in these cells which quickly lead to their death, and possible therapeutic use of these compounds in the treatment of malignant neoplasms is discussed.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid MetabolismCytotoxic aldehydes originating from the peroxidation of liver microsomal lipids
147 Citations1984Angelo Benedetti, Mario Comporti +2 more
Another cytotoxic product has been isolated and identified as 4,5-dihydroxy-2,3-decenal and its reactivities were comparable, suggesting that the production of toxic aldehydes may represent a mechanism by which lipid peroxidation causes deleterious effects on cellular functions.
Biochemical JournalEffects of diffusible products of peroxidation of rat liver microsomal lipids
133 Citations1979Angelo Benedetti, Alessandro Casini +2 more
Results indicate that during the course of the peroxidation of liver microsomal lipids toxic products are formed that are able to induce pathological effects at distant loci.
Cell Biochemistry and FunctionDNA‐damaging activity of biotic and xenobiotic aldehydes in chinese hamster ovary cells
86 Citations1984Umberto M. Marinari, Margherita Ferro +4 more
The hypothesis of a carcinogenic effect of the aldehydic products released in biomembranes during lipid peroxidation is supported.
Biochemical PharmacologyExtraction and partial characterization of dialysable products originating from the peroxidation of liver microsomal lipids and inhibiting microsomal glucose 6-phosphatase activity
81 Citations1979Angelo Benedetti, Alessandro Casini +2 more
It is concluded that lipoperoxidation products highly active in inhibiting microsomal glucose 6-phosphatase activity are fatty aldehydes or other carbonyl compounds, probably provided with a relatively long carbon chain.
Analytical BiochemistryA hydroxylapatite batch assay for quantitation of cellular DNA damage
69 Citations1979Peter M. Kanter, Herbert S. Schwartz
A batch elution procedure is described for quantitative measurement of DNA damage, which is rapid, permits large numbers of samples to be handled simultaneously, and consistently yields recoveries of >95% of total chromatographed DNA.
Chemico-Biological InteractionsInhibition of protein synthesis by carbonyl compounds (4-hydroxyalkenals) originating from the peroxidation of liver microsomal lipids
65 Citations1981Angelo Benedetti, Luigi Barbieri +4 more
Carbonyl compounds released during the NADPH-Fe dependent peroxidation of liver microsomal lipids and identified as 4-hydroxyalkenals inhibit protein synthesis in a rabbit reticulocyte lysate.
Toxicology LettersDNA damage and repair by alkaline elution in N-diazo-acetylglycine amide-treated cells
13 Citations1977M Cavanna, Silvio Parodi +5 more
The results show that DGA induces a dose-dependent damage of DNA which is repaired only slowly, and the DGA-induced damage increases for the first 2 h allowed for repair, regresses up to that displayed at the end of exposure period after 4–24 h of repair.